part s1: table of published case reports of pris between ...10.1186... · web viewck 863.000iu/l,...

Additional file 1To paper: Krajcova et al: Propofol Infusion Syndrome in 2015: A Systematic Review of Experimental Studies and 153 Published Case Reports

Content:

Part S1: Table of published case reports between 1990 and 2014 incl. complete list of references

Part S2: Step-by-step multiple logistic regression

Part S1: Table of published case reports of PRIS between 1990-2014Reference Ag

e (years)

Sex Diagnosis Purpose

of propofo

l infusion

Dosage [average

rate]

Dosage [max. rate] (hours)

Duratio

n [days]

Clinical features

Biochemical analysis

ECG changes Concomitant use of

vasopressors or corticoids

Treatment Histology/other examination

Outcome

Ugeskr Laeger1

1990

2 F Croup S 10 NA 4 day

s

Hypotension, hepatomegaly, heart failure, multiorgan failure of unknown etiology

Metabolic acidosis

NA NA NA NA Died

Parke et al.2

1992<3 F Laryngotra

cheobronchitis

S 7.5 11.5 (6)

5 (115

hours)

Fever, arrhythmia,

hepatomegaly

Metabolic acidosis, lipaemia

Nodal bradycardia with a right bundle

branch block pattern →

pharmacologically resistant asystole

NA Ionotropes (dobutamine,

dopamine, isoprenaline, adrenaline),

atropine, Tris buffer

Myocardial myocytolysis, microvesicular fatty liver,

pulmonary oedema; lumbar punction and

abdominal ultrasonography: normal;

all cultures negative

Died

<2 F Laryngotra S 7.4 8.0 3 Fever, Metabolic Nodal bradycardia NA Ionotropes: X-ray scan: bilateral Died

cheobronchitis

(29) (66 hours)

arrhythmia, hepatomegaly,

oliguria, pulmonary

oedema

acidosis, hyperkaelamia,

lipaemia

with a right bundle branch block →

asystole

dopamine, dobutamine, adrenaline,

isoprenaline, furosemide,

peritoneal dialysis, arterio-venous

haemofiltration, calcium resonium,

glucose-insulin infusion

patchy consolidation

<2 F Laryngotracheobronch

itis

S 10.0 13.6 (8)

76 hours

Fever, arrhytmia

Metabolic acidosis, lipaemia;

normal liver function and

haematologic tests

Bradycardia → procedeed to

asystole

Dexamethasoneat dose 0,5

mg/kg

Sodium bicarbonate, ionotropes, pacing

electrodes

X-ray scan: bilateral patchy consolidation; all

cultures negative; echocardiography:

normal; brain CT: normal; Histology: fatty

infiltration of liver, bilaterally consolidated lungs with histological changes (probably viral interstitial pneumonia), normal heart, with no

evidence of myocarditis

Died

<1 F Bronchiolitis

S 8.0 10.7 (5)

74 hours

Fever, arrhythmia,

hepatomegaly, acute renal

failure

Metabolic acidosis, lipaemia,

hypocalcemia –serum ionised

calcium concentration 0.68

mmol/l

Bradycardia with frequent atrial

ectopics

NA Atropine, isoprenaline,

peritoneal dialysis

Microbiology: respiratory syncytial virus in

nasopharyngeal secretion; Echocardiogram: no abnormality but viral

myocarditis was postulated

Died

6 M Laryngotracheobronch

itis

S 8.1 9.2 (1)

104 hours

Hypotension, hepatomegaly,

anuria, arrhythmia

Metabolic acidosis, lipaemic

serum

Varying PR interval,

bradycardia → leading to asystole

NA Atropine, dobutamine, adrenaline,

transvenous pacing

Microbiology: parainfluenza type 2 virus

in tracheal aspirate; sputum

sample: Pseudomonas aeruginosa. Histology: no structural abnormality of the heart, no evidence of

myocarditis, fatty

Died

microvesicular steatosis of liver, cerebral oedema, degenerative changes in

the epithelial cells of kidney;

Bodd et al.3

1992NA

NA Laryngitis S 7 NA 4 hours

NA Metabolic acidosis

NA NA NA NA Died

NA

NA Epiglotitis S NA NA 96 hours


NA NA NA NA Died

Kircpatrick et al.4

1992

<1 (1month)

F Pertussis (paroxysma

l cough, whoop,

vomiting)

S 10 NA 4 day

s

NA (no clinical

evidence of haemodynamic compromise)

Lipaemic serum; no metabolic

acidosis

NA NA Early discontinuation of propofol infusion

NA Survived

Barclay et al.5

1992

<2 (20 months)

F Acute epiglottitis

S 5-10

10 56 hours

Arrhythmia, hypotension,

oliguria, fever, generalised convulsion

Metabolic acidosis

(hyperlactatemia), lipaemic

serum, ,hyperbilirubinemia, high

levels of AST and creatine

phosphokinase ˃100,000 U/l;

myoglobinuria; leucocytosis

Bradycardia → asystolic arrest

NA Sodium bicarbonate, adrenaline,

dobutamine, adrenaline, calcium

infusions, bicarbonate, venovenous

haemodiafiltration, peritoneal dialysis

Cranial CT: normal; Microbiology:

cerebrospinal fluid – normal; Abdominal

ultrasonography: normal; Echocardiogram: normal; Microbiology: negative

blood cultures, later candidaemia; Histology –

muscle biopsy: focal necrosis with basophilic fibres and histiocytes in

skeletal muscle (no evidence of dystrophy or

neurogenic atrophy), electronmicroscopy: foci

of necrosis with some large mitochondria and

distorted cristae

Survived

Bray et al.6

19959 M Viral upper

respiratory infection

S 4.5 mg/kg/hour

6.2 mg/kg/hour

72 hours

Hepatomegaly, fever,

myocardial failure

No metabolic acidosis or

lipaemic plasma

T-wave inversion → widened ventricular

complexes →

NA Atropine, isoprenaline, dobutamine, adrenaline

Microbiology: influenza A virus in nasopharyngeal secretions. X-ray scan:

enlarged heart;

Died

bradycardia with complete heart

block → disapearance of P-waves, multifocal

ventricular complexes →

asystole

echocardiogram: impairment of ventricular function, but no structural abnormality; Histology:

mild microvesicular steatosis in the liver, some lymphocyte infiltration of

the heart, but no histological evidence of

myocarditis or damage to the conducting system

Strickland et al.7

1995

11 F Astrocytoma (surgery: frontotemp

oral craniotomy

with subtotal

removal of a grade IV astrocytom

a)

S 9.4 12 38 hours

Hypotension, fever, oliguria,

arrhythmia

Metabolic acidosis,

hyperkalemia, lipemic serum, leucocytosis,

myoglobinuria

Tachycardia → normal sinus rhythm →

junctional rhythm with tall peaked T

waves → ventricular

tachycardia and fibrillation

Dexamethasone (16 mg the first hospital day),

methylprednisolone 250 mg the second day, 50

mg the third day)

Dopamine, sodium bicarbonate,

atropine, glucose and insuline, fluid

replacement, lidocaine, calcium

chloride, bretylium, epinephrine, direct

cardioversion

CT: astrocytoma, postoperative extensive

cerebral edema; Microbiology:

Haemophilus influenzae in tracheal secretion

Died

Marinella et al.8

1996

30 F Exacerbation of asthma complicated by acute respiratory

failure

S NA NA ˂13 hours

NA Metabolic lactic acidosis; serum ketones negative

NA Methylprednisolone

Early discontinuation of propofol infusion

Microbiology: cultures of sputum, urine and blood

negative

Survived

Plotz et al.9

19966 M Laryngitis S 5-

10NA 60

hours

Heart failure, arrhythmia,

fever

Metabolic acidosis, lipaemic

serum, CK ˃ 33 000 U/l,

myoglobinuria

Nodal bradycardia andl tachycardia,

ventricular tachycardia

NA Inotropes, dantrolene

NA Died

van Straaten et

al.10

1996

4 M Laryngitis with sub-

glottic stenosis

S 8.6 NA 3 day

s

Rhabdomyolysis, pulmonary hypertension

Lipaemic serum, elevated serum carnitine, CK

127000U/l

NA NA Propofol infusion ceased, bicarbonate,

veno-venous haemofiltration

NA Survived

Bray et al.11

1998 2 NA Epiglottitis S 5.2 9 4

dayEnlarged fatty

liver, Metabolic acidosis

Bradycardia → to asystole

NA NA NA Died

s arrhythmia

1 NA Laryngitis, encephalitis

S 6.3 8.7 4 day

s

Enlarged fatty liver,

arrhythmia

Metabolic acidosis

Bradycardia, AV block

NA NA NA Died

3 NA NA S 200mg/hou

r

NA 2 day

s

An arrhythmia, resp failure

Acidosis/alkalosis NA NA NA NA Died

1 NA Croup S NA NA 2 day

s

Cardiac failure NA NA NA NA NA Died

0.5 NA Con. heart disease

S 1-6 6 3 day

s

Enlarged fatty liver,

arrhythmia

NA Bradycardia, resp failure

NA NA NA Died

8 NA Status epilepticus

S 15.2 25 29 hours

Fever, muscle rigidity,

arrhythmia

Metabolic acidosis, creatine phosphokinase

38770, myoglobinuria

Bradycardia → to asystole

NA NA NA Died

Cray et al.12

199810 months

M Viral upper respiratory infection (upper

respiratory obstruction secondary

to an esophageal

foreign body)

S 10.0 mg/kg/hour

12.8 mg/kg/hour

50.5 hours

Hypotension, arrhythmia,

enlarged liver, fever, oliguria,

olive green urine

Lipaemic plasma – high triglyceride

concentration with a normal

cholesterol level; Mixed respiratory

alkalosis and severe lactic

metabolic acidosis;

significantly increased liver transaminases,

high serum amylase,

hypocalcemia, hypoglycemia,

abnormal coagulation,

Bradycardia with first degree

atrioventricular block with right

bundle branch block → junctional

rhythm with right bundle branch block

→ sinus rhythm

NA Sodium bicarbonate, dopamine, atropine,

external transthoracic pacing, isoproterenol, fluid

replacement, epinephrine;

plasmapheresis followed by

continuous veno-venous

hemofiltration (CVVH)

Microbiology: negative bacterial cultures,

Parainfluenza III virus in nasopharyngeal aspirate;

Blood toxicology screening: propofol

metabolite; Abdominal ultrasonography: decreased liver echogenicity;

Echocardiogram: a structurally normal heart; Histology – liver biopsy:

10% zone III necrosis with fatty change – similar

to those seen in acetaminophen poisoning;

muscle biopsy: muscle necrosis associated with

Survived

leukocytosis, CPK ˃ 30 000units/L, myoglobinuria;

very large peak of lactic acid and a high level of 3-hydroxybutyrate

in urine

histiocytic response, regenerating fibers; analysis of muscle

homogenate: a reduction in cytochrome C oxidase aktivity; Skin fibroblasts culture – no underlying respiratory defect; CT

scan of the brain: normal

Hanna et al.13 1998

17 M Refractory status

epilepticus

S NA 228µg/kg/min

44 hours

Hypotension, hypoxemia, arrhythmia, fever, rusty

brown urine, anuria

Metabolic acidosis (lactate

19 mmol/L), hyperkalemia,

hypocalcaemia, creatine kinase

83,000U/L, WBC 7,900/µL,

Wide complex bradycardia with 3-

to 5- second episodes of asystole

NA Neosynephrine, dopamine, coloids,

sodium bicarbonate, calcium gluconate, atropine, dialysis

Microbiology: blood, urine, sputum specimens

cultured for bacteria sterile; Histology:

nyocytolysis of skeletal muscles, rhabdomyolysis

of the diaphragm, sediment consistent with

myoglobin filled the renal tubules; mild acute bronchopneumonia;

transesophageal echocardiography and

lower extremity venous ultrasonography – normal,

pulmonary embolism unlikely

Died


epilepticus

S NA 449µg/kg/min

63 hours

Tea-colored urine, anuria, hypotension, arrhythmia,

fever, hypoxia


24.9 mmol/L), CK 49,992 U/L, leukocytosis

WBC 24,950/µL

Tachycardia → wide complex tachycardia →

bradycardia with 3- to 5-second

episodes of asystole

Hydrocortisone Dobutamine, dopamine,

epinephrine, phenylephrine,

dialysis

Microbiology: blood, urine, sputum specimens

cultured for bacteria sterile; Chest radiograph:

no infiltrate; Echocardiography: normal left ventricular function, no evidence of elevated

right ventricular pressure – pulmonary embolism

unlikely; Histology: myocytolysis of skeletal muscles, renal tubules contained amorphous debris consistent with

myoglobin casts; patchy

Died

aspiration bronchopneumonia

Mehta et al.14 1999

18 months

F Elective surgery for

bilateral talipes

correction (arthrogryp

osis multiplex congenita)

A 6mg/kg

NA 5 hours

Oligoanuria, renal failure, arrhythmia, myocardial failure, low

oxygen saturation


3.4mmol/l), hypertriglyceridaemia 3.4 mmol/l, normal serum

concentrations of aminoacids and

organic acids; no myoglobinuria

Persistant bradyarrhythmias

NA Bicarbonate, volume resuscitation,

ionotropic support, peritoneal dialysis

Chest radiograph: consistent with acute lung

injury and pulmonary aspiration of gastric

contents; Histology – muscle biopsy: decreased

complex IV activity, lowered cytochrome oxidase ratio (0.004),

possible mitochondrial respiratory-chain enzyme deficiency; mirobiological and virological tests were

negative

Survived

Perrier et al.15

2000

18 M Trauma head injury + multiple

bone fractures

S Bolus of

220 mg +

propofol

infusion at a rate of 50-55

mg/hou

r

530-

700mg/hou

r (chyba???)

98 hours

Hypotension, fever,

arrhythmia

Metabolic acidosis, lipemic

serum, hyperkalaemia

6.4mEq/dL, increased

methemoglobin 13%,

myoglobinuria, increased creatine

kinase concentration

20,520 U/L (also due to traumatic

insult of extremities)

Sinus rhythm → atrial fibrillation

with rapid ventricular response

→ a nonspecific intraventricular

conduction block, with a possible anterolateral

infarction and a new left axis

deviation → a left bundle-branch

block with bradycardia → development of

pulseless electrical activity followed by

asystole

NA Atropine, epinephrine, fluid boluses, diuretics,

bicarbonate

Microbiology: Gram-negative bacilli in tracheal secretion; blood and urine cultures negative; Chest

radiograph: pneumomediastinum, and no change in previously

noted bilateral pulmonary infiltrates;

Echocardiography: global hypokinesis and no

evidence of pericardial effusion;

Died

Stelow et al.16

2000

47 F Exacerbation of asthma

S NA 200µg/kg/min

˂5days

Anuria, severe hypotension,

fever, arrhythmia,

darkened urine

Creatine kinase activity

762,000U/L, troponin I (cTnI)

concentration 4µg/L,

Arrhythmias and episodes of ventricular

tachycardia → cardiac arrest → supraventricular

Corticosteroids Fluid replacement, diuretics,

bicarbonate therapy, calcium

replacement, dopamine,

Chest X-ray scan: possible infiltrates; Skeletal muscle

histology: a disorganization of

myofibrils andsarcomeres. Most of the

Died

hyperkalemia, metabolic acidosis,

hypocalcemia, white blood cell count increased,

possible hematuria

rhythm phenylephrine, haemodialysis,

dantrolene

muscle fibers showed anacute necrotic reaction with swelling, loss of

striations,and vacuoles,

degeneration of nuclei.Sections of the heart

revealed numerous focal areas of myofibril

degeneration surrounded by an acute inflammatory

reaction with macrophages and

neutrophils.Presence of myoglobin

casts in ˃50%of the tubular lumen in kidney - acute tubular

necrosis

41 M Exacerbation of asthma

S NA 222µg/kg/min

˂6 day

s

Oliguria, brown urine

Serum myoglobin concentration

6800µg/L, creatine kinase

activity 204,000U/L, cTnI

46µg/L, hematuria

NA Corticosteroids Diuretic and fluid therapy

Echocardiography: globally reduced left ventricular function

without a focal lesion

Survived

Badr et al.17

200121 F Left

hemispheric

arteriovenous

malformation

(treatment: embolizatio

n of the arterioveno

us malformati

on)

S 75-150ug/kg/min

150ug/kg/min

˃48 hours

Hemodynamic deterioration

Metabolic acidosis

(hyperlactataemia), normal creatinine

measurements, serum chloride concentration 107-115 mm

NA Dexamethasone Sodium bicarbonate, dopamine

Cerebral angiography: a diffuse, left parietal

arteriovenous malformation with

hemorrhage from the anterior communicating

and middle cerebral arteries

Died

Cannon et al.18

2001

13 F Trauma head injury

S 100ug/kg/min

NA 4 day

s

Green urine, fever,

hypotension, arrhythmia, myocardial

failure, acute renal failure,

rhabdomyolysis

Leukocytosis, metabolic acidosis

(nonlactate), increased ALT, AST, creatinine

2.1mg/dl, CK MB isoenzyme

1053U/L, CK 389.000U/L,

troponin I 0.1ng/ml, total

lactate dehydrogenase

15524U/L; lactate dehydrogenase

isoenzyme 1 261U/L

Right bundle branch block → bizzare

wide QRS complexes

NA Dopamine, epinephrine, intravascular

volume support

CT of the brain: right frontal and temporal

contusion, SAH, a small right subdural hematoma;

Microbiology: Staphylococcus aureus in

tracheal aspirate; Histology – skeletal

muscle: focal necrosis of myocytes with

surrounding inflammatory cells, which was consistent with a diagnosis of focal

rhabdomyolysis; kidney: myoglobin cast

nephropathy; pneumonia, no hepatic steatosis

Died

Cremer et al.19

2001

≥ 16-

55≤

NA Head injury S 7.3mg/kg/hou

r (propofol formulation

2%)

NA ˃58 hours

NA No metabolic acidosis, no

lipaemic serum,hyperkalaemia, creatine kinase concentration >4000 U/L or

myoglobin concentration >1000 µg/L

Ventricular tachycardia

NA NA Histology: muscle-cell degradation;

Echocardiography: normal

Died

≥ 16-

55≤


r (propofol formulatio

NA ˃58 hours

NA Metabolic acidosis, no

lipaemic serum, hyperkalaemia; Creatine kinase concentration >4000 U/L or


Sinus tachycardia, supraventricular

tachycardia

NA NA Histology: muscle-cell degradation,

echocardiography: poor contractility

Died

n 2%)

≥ 16-

55≤



2%)

NA ˃58 hours

NA Metabolic acidosis,

hyperkalaemia, lipaemic serum;

Triglyceride concentrations >3·0 mmol/L

Atrial fibrillation, ventricular tachycardia

NA NA NA Died

≥ 16-55≤



2%)

NA ˃58 hours

NA Metabolic acidosis, no

lipaemic serum, creatine kinase concentration >4000 U/L or


Sinus tachycardia, idioventricular

rhythm


Echocardiography: large right ventricle

Died

≥ 16-

55≤



2%)

NA ˃58 hours


hyperkalaemia; Creatine kinase concentration >4000 U/L or


Supraventricular tachycardia, ventricular tachycardia


Echocardiography: poor contractility

Died

≥ 16-

55≤



1%)

NA ˃58 hours




Supraventricular tachycardia, nodal rhythm, ventricular

tachycardia

NA NA NA Died

≥ 16-

55≤



1%)

NA ˃58 hours




Sinus tachycardia, idioventricular

rhythm

NA NA NA Died

Wolf et al.20

2001

2 M Trauma head injury

S 5.2mg/kg

5.4mg/kg

72 hours

Oliguria, impaired renal

function

Hyperkaleamia, increased serum concentration of urea, creatinine;

metabolic acidosis (raised plasma lactate), raised

malonylcarnitine, C5-acylcarnitine, creatine kinase,

troponin T, serum triglyceride,

myoglobinaemia

Sudden and persistant nodal

bradycardia (28/min)

NA Isoprenaline infusion,

transvenous pacing, haemofiltration

NA Survived

Kelly et al.21

NA

NA Severe closed-head

S 126 ug/k

200ug/

55 hou

Renal failure, cardiovascular

Metabolic acidosis

NA NA NA NA Died

2001 (adult)

injury g/min

kg/min

rs collapse

Friedman et al.22

2002

23 F Status epilepticus

S 12mg/kg/hou

r

NA 106 hours

Arrhythmia, cardiac failure,

acute renal failure

Metabolic acidosis,

hyperkalaemia

Tachycardia NA NA NA Died

Abrahams et al.23

2002

13 M Arterio-venous

malformation

resection

A+S NA NA 4 day

s

Cardiac failure,

rhabdomyolysis, acute renal

failure

NA NA NA Propofol infusion ceased, ECMO, haemodialysis

NA Survived

Ernest et al.24 2003


S 4.1 mg/kg/hour

6.8mg/kg/hou

r

157 hours

Deterioration of renal function,

green discolouration

of urine, rhabdomyolysi

s

Creatine kinase 11,044 IU/l,

creatinine level of 0.37 mmol/l,

metabolic acidosis (serum lactate 0.6mmol/l),

lipaemic plasma

Incomplete RBBB with some peaking of the anterior T-

waves → lateral T-wave inversion →

lateral T wave inversion with

inferior flattening and some

prolongation of the QT interval →

tachycardia, slurred elevation of the ST-

T wave segments → developed into inferolateral ST

segment elevation with reciprocal

anterior changes → bizarre ST-T wave

changes and broadening of the

QRS complex, giving the

appearance of a near „sinusoidal“

rhythm → a polymorphic

NA NA CT scan of the brain: normal → sinusitis; Chest X-ray: no mediastinal or

aortic injury; Microbiology: ↑protein level, not positive for

infection; A transthoracic echocardiography

examination: normal left ventricular size associated

with moderate hypertrophy and preserved left ventricular function; An autopsy: no specific pathology to explain the

circulatory colapse, rhabdomyolysis or renal impairment, no evidence

of an undetected myocardial or aortic

injury

Died

ventricular tachycardia →

ventricular fibrillation

Kill et al.25

20037 M Osteogenes

is imperfecta

type 3 – surgical

repair of a distal femur fracture +

(minor respiratory

tract infection)

A Bolus of

120 mg, 13.5 mg/kg per hou

r

NA 150 min

NA, no fever, no

enlargement of the liver, no

bradyarrhythmias, no signs of

myocardial failure

Lactic acidosis Tachycardia Methylprednisolone

Propofol infusion discontinuation;

frusemide

Chest X-ray: no pathological

cardiopulmonary findings

Survived

Lewejohann et al.26

2004

27 M Polytrauma (severe head

trauma, multiple fractures of: rips,

extremities with severe

vascular damage, cervical vertebra,

pericardial effusion,

hematoma of the spleen, ARDS

S 25ml/

hour

10-25m

l/hod (2% propofol)

7 day

s

Severe rhabdomyolysis (initially to a

multiple trauma), renal

failure

Initial myoglobin level: 6937µg/l

(as a result of the multiple trauma),

decreased on 3865µg/l on

admission. After propofol infusion with maximum

rate 25ml/hour: a dramatic increase of the myoglobin

level to 17414µg/l…

After propofol discontinuation: myoglobin level

decreased

NA Norepinephrine, epinephrine

Hemofiltration (because of renal failure), propofol

infusion discontinuation

NA Survived

Koch et al.27

2004

5 F Endovascular coil

embolization of a

complex high output

S 15 mg/kg per h

15 mg/kg per h

10 hours

NA Lactic acidosis Bradycardia High-dose corticoid treatment; labetalol

Trigger conditions: CNS disease,

glucocorticoids, catecholamines,

beta-blockers

Chest X-ray scan: normal Survived

arterio-venous

malformation of the

right middle cerebral artery

Holzki et al.28

2004

3 F Aspiration pneumonia

S 20mg/kg per hou

r (initially

)

Re-exposure:

4.2 mg/kg per hou

r

8 hours

(re-exposure of 4.2mg/kg per hour)

Fever, hypotension,

hepatomegaly, arrhythmia

Initially: respiratory and

metabolic acidosis,

(simultaneously bronchospasm.

After re-exposure: severe metabolic acidosis; serum

glutamate oxalacetate

transaminase 2175 U/l,

serum glutamate pyruvate

transaminase 1600 U/l, creatine

kinase 2000 U/l, lactate 5.1

mmol/l; lipaemic serum

Normal rhythm after first propofol exposure → after

re-exposure: bradycardic

dysrhythmias, ventricular ectopics,

incomplete right bundle-branch

block → pronounced conduction

disturbances,broadened QRS

patterns

NA Catecholamines, insertion of cardiac

pacemaker – transvenous pacing of the

heart

Echocardiography demonstrated normal contractility; X-ray:

aspiration pneumonia; lumbar puncture: normal

Died

Withington et al.29

2004

5 months

M Operation of cleft lip and palate

A + S

11.7 mg/kg/hour

15mg/kg/hou

r

61.75 h

Hypotension, oliguria, hepatic

dysfunction, acute renal failure with

rhabdomyolysis, green brown color of urine,

arrhythmia

Lipaemic serum, lactic acidosis, coagulopathy, hyperkalemia,

hyperphosphatemia,

hypertriglyceridemia, increased levels of acetyl and hydroxy-

Wide complex tachycardia with

right bundle branch block and left axis deviation → sinus bradycardia with ventricular escape

of different morphologies → second and third

NA Isoprenaline, dopamine,

epinephrine, trancutaneous pacing without improvement…

Charcoal hemoperfusion with

success, hemodialysis

NA Survived

butyryl species with generalized elevation of fatty

acylcarnitine intermediates

(especially medium-chain

unsaturated and dicarboxylic

species)

degree heart block → ventricular tachycardia →

supraventricular tachycardia → sinus

rhythm

Culp et al.30

200413 M Resection

of parietal arterioveno

us malformati

on

A + S

Bolus of

100mg; 190µg/kg/min

NA Cardiogenic shock,

oliguria, renal failure,

rhabdomyolysis, arrhythmia

Severe metabolic acidosis, creatinine

3mg/dL, creatine kinase in the

thousands, the cardiac enzymes,

including troponin and creatine kinase MB

isoenzyme, were within normal

limits; myoglobinuria;Hemolysis, a

mild unconjugated hyperbilirubin

emia(2–3 mg/dL) (consistent

with continuinghemolysis)

Sinus rhythm with a normal QT interval → prolonged QT

interval and T wave inversions → polymorphic ventricular

tachycardia → accelerated junctional

tachycardia → normalization of cardiac rhythm

(sinusrhythm with a

normal QT interval)

No steroids Cardioversion, IV magnesium and

potassium supplementation,

lidocaine and amiodarone infusions,

epinephrine, norepinephrine,

bicarbonate;Extracorporeal circulation with

membrane oxygenation

CT scan of the brain: brain edema; Transthoracic

echocardiogram: severe biventricular dysfunction, no pericardial effusion, no

significant valvular disease →

transesophageal echocardiography:

normal biventricular function; Chest film:

pulmonary edema

Survived

Baumeister et al.31

2004

10 M Status epilepticus (fasting for two days, a

classic ketogenic

diet: 55kcal/day,

S 5.5-9

mg/kg/hour

9 4 day

s

Cardio-circulatory instability,

fever, rhabdomyolysis, progressive

respiratory insufficiency,

Hyperlipidemia (serum

triglycerides 5200mg/dl; serum

cholesterol 440mg/l),

rhabdomyolysis (maximum of

Right bundle-branch block,

ventricular arrhythmia → polymorphic ventricular

tachycardia (torsade de pointes) → after

NA Lidocaine, magnesium,

dopamine, stopping of propofol infusion and ketogenic diet;

glucose-insulin-infusion; esmolol, catecholamines,

NA Died

containing 90% of

energy as long-chain triglycerides (3 days)

congestive heart failure, arrhythmia

serum CK 18 900U/l, CK-MB

isoenzyme 700U/l,

pigmenturia), metabolic acidosis with a lactate of

6.4 mmol/l

treatment by lidocaine and magnesium it

disappeared → bigeminal rhythm

and salves of ventricular

extrasystoles → after esmolol sinus

rhythm → ventricular

tachycardia → ventricular fibrillation

ajmalin

Casserly et al.32

2004

42 M Cerebral sinus

thrombosis, cerebral

hemorrhage,

hydrocephalus

S NA 143 µg/kg/min

3 day

s

Acute renal failure, anuria,

myocardial dysfunction, arrhythmia

Creatinine level ˃ 451µmol/L, blood

urea nitrogen levels 9.9mmol/L, serum bicarbonate

14mmol/L, metabolic

acidosis, CK 22.426U/L, serum

myoglobin 230mg/dL,

troponin 20µg/L

Right bundle branch block with diffuse

ST and T-wave changes →

asystolic arrest

Phenylephrine (to maintain

adequate cerebral

perfusion pressure)

Fluid resuscitation - aggressive hydration(and urine

alkalization), norepinephrine

NA Died

17 F Polytrauma (including head injury

– closed head

contusion) –

intraabdominal

hemorrhage (owing to splenic, hepatic,

pancreatic, bladder, and right

S NA 118 µg/kg/min

5 day

s

Rhabdomyolysis, oliguria

CK 172.833U/L, serum creatinine

512 µmol/L, blood urea nitrogen

16mmol/L,hyperkalemia

5.6mmol/L, bicarbonate

18mol/L, normal troponin levels, urine myoglobin

negative

Diffuse ST and T-wave changes

Phenylephrine Renal replacement therapy,

hemodialysis

CT scan of the brain: cerebral edema without

herniation;

Survived

colonic mesentery

lacerations)

Burow et al.33

2004

31 F Radiofrequency

ablation of chronic atrial

fibrillation

A 83 µg/kg/min

125 µg/kg/min

˃ 6 hours


NA NA Early discontinuation of propofol, sodium

bicarbonate

Echocardiography: normal ventricular function with a

left ventricular ejection fraction of 55% and mild

atrial enlargement;

Survived

Salengros et al.34

2004

71 M Laparoscopic radical

prostatectomy

A NA 7.8mg/kg/hou

r

˃ 4.5 hours

Arrhythmia Metabolic acidosis

Tachycardia NA Early discontinuation of

propofol

Transesophageal echocardiography: good

left and right contractility, adequate

ventricular filling, and an adequate cardiac output;

Microbiology: blood cultures negative; the abdominal cavity was

searched for anyseptic source or hepatic

necrosis, without success.

Survived

Haase et al.35 2005

7 M Craniosynostosis

admitted following

surgery (11 hours fasting before

anesthesia)

A 100 mg bolu

s (total

dose

6.1 mg/kg

BW)

NA 40 minutes

↑CK ← surgical

trauma or subclinical

rhabdomyolysis; Hypotensio,

arrhythmia

Metabolic acidosis (lactate 9.4 mmol/l), CK 5.27 µmol/lxs;

myoglobin, glutamate

oxaloacetatetransaminases,

and triglycerides –normal range,

urine examinationand urinary output

– normal.

Tachycardia NA Early discontinuation of propofol infusion

NA Survived

Liolios et al.36

2005

42 M Brainstem cavernous angioma

A + S

5.2 (1

hour) –9

mg/

9 mg/kg

38 hours

Renal function impairment

Lactic acidosis 10.8 mmol/L, CK 3470 IU/L, serum

creatinine 1.6 mg/dL, absent

ketonuria;

ECG without abnormalities

Methylprednisolone

Early discontinuation of propofol infusion

NA Survived

kg/hour (3

hours)

Serum potassium concentration – normal; urinary

output was adequate

Kumar et al.37

2005

27 F Seizures secondary

to hemorrhage

from an arterioveno

us malformati

on

S NA NA ˃36 hours

Hypotension, arrhythmia

Metabolic (lactic) acidosis, creatine

phophokinase 37.749 U/L,

hyperkaelemia, normal troponin and myoglobin

level

Wide complex bradycardia →

asystole

NA Fluid resuscitation, epinephrine,

dopamine, sodium bicarbonate, calcium

chloride, transvenous pacemaker

CT of the brain: a large intraventricular

hemorrhage; echocardiogram: lateral

ventricular wall ischemia; microbiology: all cultures

negative

Died

64 M Status epilepticus

S NA NA ˃24 hours


Metabolic acidosis

(pH=7.16), CPK level 48.000U/L

Bradycardia with a junctional rhythm

→ asystole

NA Neosynephrine, dopamine,

bicarbonate, calcium

Microbiology: all cultures negative

Died

24 F Status epilepticus secondary

to encephalitis

S NA NA ˃24 hours


Metabolic acidosis,

hyperkaelemia, hypocalcemia

Bradycardia → pulseless electrical

activity

NA Dopamine, transvenous pacing, sodium bicarbonate,

insuline with dextrose, calcium

chloride

CT of the brain: normal; microbiology: all cultures

negative

Died

Machata et al.38

2005

40 M Trauma head injury, fractures of

the fifth cervical

vertebra + 6 weeks

after trauma: septic

shock – cause of

death (multiresist

ant Pseudomon

A+S 3 (during sedation

)

3 (during sedation

)

˃ 72 hours

Fever 41°C, darkened

urine, anuria, renal

insufficiency

Serum creatine kinase 708.04 nmol/L, serum

myoglobin 4625.1 nmol/L, creatinine

0.48 mmol/l, hyperkalemia 5.9

mmol/L, metabolic acidosis

NA NA Continuous veno-venous

hemofiltration, dantrolene; Serumpotassium and

body temperature

could be normalized

rapidly under hemofiltration.

Serum myoglobin and

CK alsodecreased)

Chest X-ray: no infiltration; microbiology:

no infection in blood cultures; microscopic

examination of skeletal muscle: muscle fibers with signs of vacuole

formation and cytochrome-oxidase-

negative fibers; Biochemical examination of the muscle fibers: an increase in free carnitine

and NADH-CoQ-oxidoreductase (may be

an indicator for a

Died (later septic

complications)

as aeruginos

a)

metabolic myopathy)

Suen et al.39

200631 M Thoracosco

pic wedge resection

(lung biopsy of suspicious tumor) +

minithoracotomy →

adult respiratory

distress syndrome

S NA (range

7.5-13.75)

13.75

5 day

s

Greenish color urine,

arrhythmia, hypotension, acute renal

failure, anuria, fever,

cardiovascular collapse

Urinanalysis: no hemoglobin, no

infection; elevation of total CK 257.500 U/L,

CK-MB 156.2 ng/mL, troponin-

T 0,09 ng/mL, severe metabolic acidosis (elevated

lactate), hyperkalemia, creatinine 3.7

mg/dL, calcium 1.13 mmol/l,

serum glutamic pyruvic

transaminase 304 U/L, serum

glutamic oxaloacetic

transaminase 1094 U/L,

phosphorus 7.76 mmol/L

Severe ST-segment elevation → ventricular

tachycardia and fibrillation →

junctional rhythm, widened QRS complex and bradycardia

NA Resuscitation, cardioversion,

transvenous pacing, inotropics, fluid, diuretics, sodium

bicarbonate, dantrolene

Chest radiography: new right upper zone infiltrate

→ increasing bilateral ground

glass opacities.; echocardiography: normal

cardiac function; Emergency cardiac

catheterization: insignificant coronary

artery disease; Histology: a lipemic appearance of

the blood, rhabdomyolysis of the diaphragm,

quadriceps, and psoas muscles, cardiomegaly,

hepatomegaly with steatosis, and splenomegaly

Died

Eriksen et al.40

2006

20 F Osteosynthesis after trauma – multiple

fractures – bilateral femoral

fractures, fractures of

the mandibular

and the maxilla, a

minor

S (not during A)

4.5-5.1mg/kg/h

NA5.1?

?

5 day

s

Green color of urine,

hemodynamic instability, no

signs of compartment

syndrome, rhabdomyolysis, arrhythmia

CK 52.295 IU/l, myoglobine 1030

µg/l, CK-B 18 IU/l, troponin 3.1 µg/l, creatinine

158 µmol/l, hyperkalemia, no

metabolic acidosis, normal liver, pancreas

and coagulation blood samples

Ventricular tachycardia

Dopamine 6 mg/kg/min

Sodium bicarbonate, dopamine,

norepinephrine, forced alkalized

diuresis, furosemide, lidocaine,

amiodarone

Initial brain scan: normal; chest X-ray: normal;

microbiology: pulmonary secretion, blood and urine: normal; Later CT scan of

the head, thorax and abdomen: a superficial

intracerebral bleeding and slight cerebral oedema,

bilateral basal atelectasis of the lungs;

echocardiography: no pericardial effusion;

Histology: a normal-sized

Died

pneumothorax and a

slight contusion

of both lungs;

fractures of the dens axis, the

right occipital condyle, and the

right articular

process of the 4th

cervical vertebra

suspected

brain with increased volume of the gyri and

three superficial intracerebral bleedings in the grey matter, normal-

sized lungs without contusion, blood or

secretion, but with a firm consistence, normal heart, liver, pancreas and spleen;

normal kidneys, but a little pale with increased fluid content; no necrosis

of myocardium, but a slight interstitial and

perivascular fibrosis and a small bleeding in the

tissure; no fatty infiltration of the liver; Toxicology: traces of

propofol in the liver tissue ; cause of death: multi-

organ failure

Vernooy et al.41

2006

15 M Head injury S 4.5mg/kg/hou

r

NA 6days

Rhabdomyolysis, fever,

arrhythmia

Myoglobinuria, creatine kinase

92,300U/L, creatinine

265µmol/L

ST-segment elevation in the right precordial

leads (Brugada like ECG patern) and inverted T waves; after withdrawal of

propofol ST segment elevations normalized over the

following hours, inversion of T

waves persisted; no evidence of arrhythmia

Concomitant administration of

dopamine, norepinephrine;

(to maintain cerebral

perfusion pressure)

Early withdrawal of propofol infusion

Screening of DNA mutation performed

(SCN5A8) → inherited form of ST-segment elevation excluded

Survived

17 F Head injury S 7.3 NA ˃58 hours

Fever, arrhythmia

Hyperkalemia ˃5.5mmol/l

Brugada-like ECG pattern

→ventricular tachyarrhythmia

- - Died

→ventricular fibrillation

44 M Head injury S 5.7 NA ˃58 hours

Fever, severe hypotension, arrhythmia

- Supraventricular tachycardia with poor ventricular

contractility

Ventricular pacing - Died


Arrhythmia - Brugada-like ECG pattern



- - Died






- - Died


Arrhythmia - Brugada-like ECG pattern



- - Died


Fever, arrhythmia

Hyperkalemia ˃5.5mmol/l




- - Died


Arrhythmia Metabolic acidosis,

hyperkalemia ˃5.5mmol/l




- - Died

Merz et 24 M Spinal S 1.9 2.6 ˂4 Acute renal Increased cardiac Bradycardia Concomitant use NA NA Died

al.42

2006injury,

aspiration, ARDS, SIRS

days

failure, rhabdomyolysi

s, massive cerebral edema,

arrhythmia

troponin I 6,3ng/mL and creatine kinase 486,900U/L, hyperkalemia

of large-dose methylprednisolone + moderate

adrenergic support

(dopamine, norepinephrine)

Corbett et al.43

2006

21 M Traumatic brain injury

S 1.9-12

12 3 day

s

Oliguria, transient renal insufficiency,

arrhythmia

Metabolic acidosis (lactic

level 10.9mmol/l), creatinine 1.3mg/dL,

creatinine kinase 3076µ/L

Sinus tachycardia → normal sinus

rhythm

Concomitant use of high-dose vasopressor

therapy (dopamine,

norepinephrine, phenylephrine)

(to maintain CPP)

Therapy with metoprolol,

captopril, early withdrawal of

propofol

CT of the head: a comminuted

depressed skull fracture of the

right frontal bone, with a subdural hematomaand interventricular hemorrhage; plain

films of the chest and pelvis and computedtomography of the

abdomen andpelvis: negative;

Echocardiogram: severe global left ventricular

dysfunction and moderate global dysfunction of the

right ventricle → resolution of

cardiomyopathy

Survived

Hermanns et al.44

2006

16 F Scoliosis surgery (in patient with

neonatal progeroid syndrome)

A 9.1 NA ˃6.5 h

Darkish urine, hypotension, arrhythmia

Urine myoglobin concentration

1660µg/l, metabolic (lactic)

acidosis

Tachycardia → atrioventricular

nodal rhythm (nodal tachycardia) →

tertiary AV block with a ventricular heart rate of 10-20 beats/min → sinus

rhythm

Concomitant use of

norepinephrine

Therapy by verapamil → epinephrine,

atropine, orciprenaline

NA Survived

Tramptisch et al.45

2006

66 NA Postoperative period

after aortocoronary bypass

S 1-3 mg/kg/h with bolu

3 9 day

s

Hepatomegaly?, arrhythmia

↑ lactate 4.1 mmol/l,

myoglobin 12.467 µg/ml, creatin

kinase 27.580 U/l,

Paroxysmal atrial fibrillation

Noradrenalin, dobutamin

Discontinuation of propofol

CT: lesion in the periventricularmedullary and hepatomegaly

Survived

ses serum creatinine 2.64 mg/dl,

kalium 5,4 mmol/l

Chukwuemeka et al.46

2006

45 M Coronary artery bypass grafting

A+S 44µg/kg/min + 80 mg bolu

s

44µg/kg/min

˂ 10 hours


Metabolic (lactic) acidosis

Sinus tachycardia with widespread ST segment elevation

→ ventricular tachycardia

Dopamine Fluid resuscitation, intravenous calcium chloride, adrenaline,

electrical direct current

cardioversion, amiodarone, epinephrine,

hydrocortisone, diphenhydramine,

sodium bicarbonate; withdrawal of

propofol

Echocardiography: good left ventricular, no cardiac

valvular pathology; → transoesophageal

echocardiography: good biventricular contractility and adequate ventricular

filling;

Survived

De Waele et al.47

2006

30 M After laparotomy

for drainage of

an abdominal

abscess (quadriplegic patient) + bilateral

Pseudomonas

aeruginosa pneumonia

S 5.7 (2%

)

5.7 56 hours

Arrhythmia Increased troponin T

(0,16ng/ml), creatine

phosphokinase 9008IU/l, lactate

(19mg/dl)

Sinus arrhythmias and intermittent atrial fibrillation, inferolateral T-

wave inversion → cardiac arrhythmias

disappeared after discontinuation of propofol infusion

Concomitant use of

norepinephrine

Withdrawal of propofol

Transthoracic echocardiography:

normal, no pericardial effusion; Microbiology: bilateral Pseudomonas aeruginosa pneumonia

Survived

Sabsovich et al.48

2007


S 1.66-

8.33

8.33 3 day

s

Rusty brown urine, acute renal failure, hypotension, arrhythmia

Creatinine 371µmol/L, Metabolic

acidosis (pH 7.1), bicarbonate

10mmol/L, CPK 251762U/L,

aspartate aminotransferase 3082U/L, alanine aminotransferase

Left bundle branch block with diffuse changes in the ST segment and the T wave → new onset of diffuse changes in the ST segment

and T wave → wide-complex tachycardia → bradycardia →

Concomitant use of phenylephrine

Treatment by aggressive hydration,

bicarbonate infusion, fluid resuscitation;

discontinuation of propofol;

Echocardiography: normal myocardial infusion

Died

1144U/L, lactate dehydrogenase 4687U/L, MB

fraction of CPK 333.5U/L, troponin

17.39ng/mL

asystole

Westhout et al.49

2007

3 F Angiographic

embolization

(aneurysm in the left internal carotid artery)

A + S

Bolus of 80 mf propofol

(for 3

hours) +

200 µg/kg/hr (4 hours)

200 µg/kg/h

r

8 hours


Metabolic acidosis, CK 591

U/L, lactate dehydrogenase 179 U/L, lactate 1.1 mmol/L; the

blood urea nitrogen 11 mg/dl,

creatinine 0.6 mg/dl, normal salicylate and ammonia; a

creatine phosphokinase2 - myoglobin level of 20.7

ng/mland a relative index of 3.5

.

Tachycardia NA Bicarbonate, aggressive fluid

resuscitation with 5% albumin,

vasopressors, 5 mg dexamethasone

NA Survived

Zarovnaya et al.50

2007


S 4.2-7.2

7.2 64 hours

Dark urine, fever,

hypotension, decreasing

urine output, arrhythmia

CPK 150.000U/L, metabolic (lactic) acidosis, elevated serum creatinine

Pulseless electrical activity → asystole followed by wide

complex tachycardia →

diffuse low voltage, diffuse T-wave

flattening, normal QT → wide QRS

complexes → bradyarrhythmia →

asystole

NA Treatment by aggressive

resuscitation including

defibrillation, pacing,

hemodialysis, phenylephrine,

vasopressin, dobutamine

Biopsy of skeletal muscle: acute aseptic necrosis,

consistent with rhabdomyolysis; myocyte swelling, loss of striation,

vacuole formation, interstitial edema, variable myocyte hypertrophy; red

myoglobin casts in the dilated tubules; congestion

of the lungs, liver and spleen

Echocardiogram: global biventricular dysfunction

Died

Karakitsos et al.51

2007

35 F Head injury S 25-30ml/h

(2% propofol)

30ml/h

4 day

s

Acute renal failure with concomitant myocardial dysfunction

Metabolic acidosis,

hyperkalaemia 6.2mmol/l,

creatine kinase 42.000U/l, myoglobin 2100µg/l, lipaemia

4.1mmol/l

NA Concomitant use of vasopressors

Therapy by haemofiltration,

early withdrawal of propofol

Transoesophageal echocardiography: global

left ventricular hypokinesia

Survived

Rosen et al.52 2007

18 M Trauma brain injury

S NA 7,5 ˃72 hours

Dark urine, anuria,

worsening hemodynamics, arrhythmia

Creatine phophokinase

95.440U/L, serum creatinine 3.6g/dL,

metabolic acidosis pH 7.1

Cardiac arrhythmias → asystole

Low-dose vasopressors

Resuscitation NA Died

29 F Trauma brain injury

S 4-12

12 6 day

s

Hypotension, cardiovascular

collapse

Metabolic (lactic) acidosis 7.01,

CPK 6.966U/L, myoglobinuria

Cardiovascular collapse

Concomitant use of epinephrine

Treatment by discontinuation of

propofol (with thiopental),

phenylephrine, aggressive

intravascular volume support

NA Died

Bordes et al.53

2008

66 NA Glioblastoma

A 6.9 7.6 5 hours

NA Hyperlactataemia NA Concomitant use of steroids

Discontinuation of propofol infusion

NA Survived

Fudickar et al.54

2008

21 F Cerebellar bleeding +

surgical decompression of the occipital cranium

S + A

5.7 mg/kg/hour (2%

)

5.7 5 day

s

Arrhythmia CK 5194 U/L, CK-MM 29424 U/L, myoglobin

4880 µg/L, normal lactate,

sodium bicarbonate and pH, increased

AST and ALT, GGT, amylase

and lipase, normal bilirubin, serum

Ventricular ectopic beats and ST-

segment depression in leads II, III and

aVF;

Concomitant use of

norepinephrine. hydrocortisone

Discontinuation of propofol and

replacement by midazolam, amiodarone

Digital subtraction angiography: arteriovenous

malformation of the brain stem; Ultrasound liver scan: no signs of liver

damage; Brain magnetic resonance imaging (MRI):

no ischaemic damage; Brain stam acoustic

evoked potentials and somatosensory evoked

Survived

creatinine, serum urea and urinary

output

potentials: normal

Romero et al.55

2008

43 F Brain surgery due

to a vascular

malformation

A+S 3.5-7

7 15 hours (7

hours

anaesthesia, 8 hours

sedation

)

NA Metabolic (lactic) acidosis

ECG without abnormalities

Concomitant use of

catecholamines and

corticosteroids

Discontinuation of propofol, treatment of norepinephrine, fluid resuscitation

NA Survived

Shimony et al.56

2008

52 M Cardiac arrest –

stenting of an occluded

proximal left anterior descending coronary

artery

S NA 400mg/hou

r

7 day

s

Acute renal failure,

rhabdomyolysis

Hyperbilirubinemia, elevated liver

enzymes (alanine aminotransferase 206U/L, aspartate aminotransferase 828U/L), creatine

kinase 42.700, creatinine 7.6mg/dl, metabolic acidosis,

hyperlipaemia (triglycerides 3050mg/dl)

Initially: anterior wall ST elevation

NA Discontinuation of propofol and

replacement by midazolam,

hemodiafiltration

Initial echocardiography: severe left ventricular

dysfunction

Survived

Robinson et al.57

2008

9 months

M Status epilepticus

S Bolus + 14mg/kg/hou

r

14 ˂ 3days

Arrhythmia CK 21.000U/L, mild metabolic

acidosis (bicarbonate

15mmol/L, lactate 3.5mmol/L),

creatine kinase muscle brain

Slow sinus mechanism with low-amplitude P

waves, first-degree atrioventricular

block, low ventricular voltages, a slightly widened

NA Stopping propofol; Treatment by

lidocaine, adenosine, atrial

overdrive pacing via the esophageal

electrode, synchronized direct

Echocardiography: normal biventricular function and

no structural defects` Cranial magnetic

resonanceimaging revealed a mild Chiari I malformation

and changes in the right

Survived

isoform (CKMB) relative index

3.1%, troponin T 0.03ng/mL

QRS complex consistent with right

ventricular conduction delay,

nonspecific ST and T-wave changes,

escape beats with a slightly different QRS morphology → progression of

the intraventricular conduction delay to

complete right-bundle-branch

block → diffuse abnormalities (markedly low voltages and

irregular QRS pattern with

complete right-bundle-branch

block), AV conduction with first and second

degree AV block → sustained wide-

QRS tachycardia with left-bundle-

branch-block morphology →

after cardioversion: irregular pattern with the baseline QRS morphology

of the right-bundle-branch block with some premature beats and short

salvos of tachycardia with a left-bundle-branch

block QRS morphology;

current cardioversion with 1.5 J/kg, lidocaine

infusion

thalamus consistent withprolonged seizure activity,

but no major pathology.

diffuse conduction disturbances

complicated by ventricular

tachycardia of right-ventricular origin with a left-bundle-branch block QRS

morphology; Lidocaine infusion:

episods of ventricular

tachycardia; sinus rhythm with

improved voltages and less

intraventricular conduction delay,

dramatic ST elevation in lead V1 in a pattern similar

to Brugada syndrome → ECG

normalized

Zaccheo et al.58

2008

33 F Trauma head injury

S 20-190µg/kg/min

190µg/kg/min

6 day

s


Serum triglyceride level

11.420mg/dL, metabolic acidosis

(pH 7.17, bicarbonate

8.9mEq/L, lactic acid 12.5mg/dL),

total creatine kinase 18.333U/L,

myoglobin 18.470ng/mL

Normal sinus rhythm with a first-

degree atrioventricular

block, left anterior hemiblock, right

bundle branch block → wide-complex ventricular rhythm → tachycardic and

bradycardic rhythms → cardiac arrest with pulseless

electrical activity

Concomitant use of

norepinephrine

Treatment by fluid replacement and norepinephrine,

epinephrine, sodium bicarbonate, transvenous pacemaker,

discontinuation of propofol

Computed tomography ofthe head showed a right

temporalsubdural hematoma and a

subarachnoidhemorrhage.

Died


(alcohol withdrawal

S Bolus of

1mg

140µg/kg/min

48 hours

Hypotension, acute oliguric renal failure,

shock,

Metabolic acidosis (lactic

acid 8.4mg/dL pH 7.34, bicarbonate

NA Norepinephrine Crystalloid/colloid volume

replacement, norepinephrine,

NA Died

seizures) /kg +

infusion of

120-

140µg/kg/min

rhabdomyolysis

14.1mEq/L), myoglobin

210.030ng/mL, CK 69.175U/L,

serum triglyceride 628mg/dL

continuous renal replacement therapy

Aloizos et al.59

2008

20 M Upper airway

obstruction due to

Epstein-Barr

infection

S 2.14-

5.71

5.71 4 day

s

Rhabdomyolysis, acute renal

failure with oliguria

progressing to complete anuria → polyuria

CPK ˃7000iu/lt, creatinine 7mg/dl, no sign of lactic

acidosis

NA (without a signs of heart failure)

NA Hydration, bicarbonate

administration, replacement of propofol with midazolam,

continuous veno-venous

haemodiafiltration dialysis

Bed side abdominal ultrasonography: mild

liver and spleen enlargement;

Microbiology: blood, urine and broncho

alveolar lavage (BAL) cultures negative.

Abdominalcomputed tomography

(CT) findings: consistentwith the EBV infection.

Survived

Laquay et al.60

2008

12 F Surgical correction

of congenital

mitral regurgitatio

n on a mitral cleft

with normother

mic cardiopulm

onary bypass (CPB)

A ˂3mg

˂3mg

15 hours

NA Metabolic acidosis (lactate

9.3mmol/l)

NA Concomitant use of epinephrine

Treatment by sodium bicarbonate,

early cessation of propofol infusion

Transoesophageal echocardiography at the

end of surgery: a balanced contractility of the two

ventricles and the lack of residual mitral regurgitation

Survived

16 F Surgical correction

of

A ˂3mg

˂3mg

8 hours

NA Metabolic acidosis (lactate

14.7mmol/l)

NA Concomitant use of epinephrine

Treatment by sodium bicarbonate,

early cessation of

Transoesophageal echocardiography at the

end of surgery: a balanced

Survived

congenital mitral

regurgitation on a

mitral cleft with

normothermic

cardiopulmonary bypass (CPB)

propofol infusion contractility of the two ventricles and the lack of

residual mitral regurgitation

Smith et al.61 2009


A+S A:50-

75mcg/kg/minS: 95-125mcg/kg/min

125mcg

/kg/min

˃85 hours

Cardiac complications

Mild metabolic acidosis, CK

12.858U/l, CK-MB 59.5ng/ml, LDH 618U/l,

troponin 0.9ng/ml

T-wave inversion and prolonged QTc

intervsl

Concomitant use of phenylephrine

Treatment by dobutamine,

replacement of propofol with a

midazolam

Echocardiogram: a left ventricular ejection fraction of 40-45%

Survived


S 75-125mcg

/kg/min

125mcg

/kg/min

89 hours

Arrhythmia CK 5.111U/l, CK-MB 30.9ng/ml,

LDH 409U/l

ST elevation and tachyarrhythmias → polymorphic

ventricular tachycardia → spontaneously

reverted to normal waveform

morphology 12 h after stopping

propofol

Concomitant use of

phenylephrine, dopamine

Treatment by replacement of propofol with a

thiopental infusion

Echocardiogram: preserved left ventricular ejection fraction of 55-

60%

Survived


S 30-134mcg

/kg/min

134mcg

/kg/min

135 hours

NA CK ˃25.300U/l, metabolic

acidosis, CK-MB 17.8ng/ml, troponin

0.7ng/ml, LDH

Inverted T waves Concomitant use of phenylephrine

Treatment by replacement of propofol with a pentobarbital

infusion

NA Died

1.098U/l, positive urine myoglobin

Ilyas et al.62

200967 M Coronary

artery bypass grafting (CABG)

using cardiopulm

onary bypass +

atrial fibrillation

A 0.8-5.2

5.2 7,5 hours

NA Metabolic acidosis (lactic

acid 13.3 mmol/L),

myoglobinuria, hemoglobinuria,

no ketonuria, creatine kinase

260 mmol/L, withpredominant

skeletal muscle expressed fraction

of creatinekinase CK-MM, normal troponin,

liver enzymes

No electrocardiographi

c abnormalities

Concomitant use of epinephrine;

Preoperative medications: prednisolone

Discontinuation of propofol infusion

Initial transoesophageal echocardiography: mild

left ventricular dysfunction;

Survived

Veldhoen et al.63

2009

17 M Multiple skull

fractures – trauma

S NA (range 3-8 mg/kg/h

)

Max. 8 mg/kg/hrfor a

total of14 hours

4 day

s

Oliguria → progressive

cardiac failure with anuria

and rhabdomyolysis, arrhythmia

Progressive lactic acidosis, ↑ CK 7476 U/L; ↑

acylcarnitine C2 22.9 µmol/L,

and ↑ C4 0.46µmol/L

Tachycardia, cardiac failure

Ionotropic support

Discontinuation of propofol, high

carbohydrate intake, high doses of

inotropic support, repeated

resuscitation; mechanical cardiac support with intra-

aortic balloon pump: failed because of

tachycardia

Initialcomputerized tomography

scan of thebrain: no abnormalities → generalized edema of the brain; Microbiology: blood cultures negative;

Histology: cerebral edema, no signs of

pneumonia; Microscopy of the muscles: no features

of degeneration, but enzymatic and histochemical

abnormalities of acute muscle degeneration present, mild liver

steatosis, contraction band necrosis in myocardial

cells

Died

Orsini et al.64

2009

36 F Respiratory failure and

sepsis,

S 3.5-6

6 8 day

s

Morbilliformrash on the

neck,

Hypertriglyceridemia 1.005mg/dL, increased amylase

Sinus tachycardia Concomitant use of

norepinephrine,


Computed tomography of abdomen: hepatomegaly with fatty infiltration of

Survived

likely secondary

to pneumonia

shoulders, chest, dark-green urine,

hepatomegaly, arrhythmia

294U/L, lipase 608U/L, creatine

kinase levels 36.327U/L,

abnormal liver function test values (AST 115U/L,ALT 536U/L, γGT 501IU/L), pH 7.42, normal troponin level

vasopressin, hydrocortisone;

liver; Transthoracic echocardiogram: normal left ventricular function

Iyer et al.65

2009NA (range: 31-

77)


S NA (range: 10-118µg/kg/min

)

NA (range:50-

200 µg/kg/min

)

NA (range: 36-391 hours)

NA (occurrence of one or more of the following:

metabolic acidosis,

rhabdomyolysis, bradycardia, heart failure,

hyperkalemia, renal failure, lipemia, other arrhythmias and death)

NA Without cardiac arrest

NA NA NA Survived

NA (range: 31-

77)



)

NA (range:50-

200 µg/kg/min

)



metabolic acidosis,




NA NA NA Survived

N M Status S NA NA NA NA NA Without cardiac NA NA NA Survived

A (range: 31-

77)

epilepticus (range: 10-118µg/kg/min

)

(range:50-

200 µg/kg/min

)

(range: 36-391 hours)

(occurrence of one or more of the following:

metabolic acidosis,



arrest

NA (range: 31-

77)



)

NA (range:50-

200 µg/kg/min

)



metabolic acidosis,




NA NA NA Survived

NA (range: 31-

77)



)

NA (range:50-

200 µg/kg/min

)



metabolic acidosis,




NA NA NA Survived

NA (range: 31-

77)



)

NA (range:50-

200 µg/kg/min

)



metabolic acidosis,




NA NA NA Survived

NA (range: 31-

77)



)

NA (range:50-

200 µg/kg/min

)



metabolic acidosis,




NA NA NA Survived

NA (range: 31-

77)

F Status epilepticus


)

NA (range:50-

200 µg/kg/min

)



metabolic acidosis,




NA NA NA Survived

NA (range: 31-

77)



)

NA (range:50-

200 µg/kg/min

)



metabolic acidosis,




NA NA NA Survived

NA (range: 31-

77)



)

NA (range:50-

200 µg/kg/min

)



metabolic acidosis,




NA NA NA Survived

NA (range: 31-

77)



)

NA (range:50-

200 µg/kg/min

)



metabolic acidosis,




NA NA NA Survived


S 140µg/kg/min

140µg/kg/min

4 day

s

Fever 38,4°C, diminished

urine output, hypotension, arrhythmia


2.4mmol/L), elevated ALT and

AST values, myoglobinuria

Tachycardia → widened QRS

complex (QTc 549 msecs), right bundle

branch block, junctional rhythm,

bradycardia → ventricular

tachycardia → ventricular

fibrillation → asystolic cardiac

arrest

NA Aggressive fluid and pressor resuscitation

Microbiology: Blood cultures obtained on

arrivalnegative.

Died


S 70-175µg/kg/min

175µg/kg/min

66 hours


Metabolic acidosis (pH

7.26), elevated CK 3.538U/L, elevated liver function tests (ALT 94U/L, AST 187U/L),

elevated triglyceride 720mg/dL

Incomplete right bundle branch block

with a prolonged QTc (546msesc)

along with T-wave inversions in the

inferior limb leads and lateral

precordial leads → a markedly changed

rhythm with complete right bundle branch

block, bradycardia, QRS prolongation, junctional rhythm, greatly magnified T-wave inversions → wide, complex, pulseless electrical

state

NA Treatment by phenylephrine, norepinephrine,

epinephrine treatment,

immediately stopping of propofol

Echocardiogram: normal sized right and left

ventricles and a calculated LVEF of 30%

Died


S 17-110µg/kg/min

110µg/kg/min

˃ 3.5 day

s

Hypontesion, arrhythmia

NA Sinus bradycardia, a very prolonged QTc interval (720msecs), and widespread T-

wave inversion → a wide complex

tachycardia resembling torsades

NA Stopping of propofol and

replacement by midazolam,

cardiopulmonary resuscitation with magnesium and an advanced cardiac

NA Survived

de pointes life support protocol

Mali et al.66

200948 F Thoracosco

pic esophagect

omy for carcinoma

of the esophagus

A 3 (+bolus of

1mg/kg/hour)

3 4 hours

Arrhythmia Serum potassium 8.2mmol/L, pH

7.33 (not considered as acidosis by authors),

myoglobinuria

Tall T waves, flattened P waves,

widened QRS complex, episode of

bradycardia → taller T waves, wide

QRS complex, absent P waves →

QRS widening decreased

NA Treatment by atropine, calcium gluconate, sodium

bicarbonate, glucose with insulin

NA Survived

Blum et al.67

2009

40 M A type B aortic

dissection (after

stenting of the superior mesenteric, renal, and

iliac arteries)

S 50-90µg/kg/min

90µg/kg/min

˃5 day

s

Arrhythmia Slightly elevated lactate without

acidosis, elevated CK 18.902IU/L,

urinary myoglobin

66IU/L, troponin 51.6ng/ml

Elevated ST segments

throughout → multiple periods of unstable ventricular

tachycardia (requiring ACLS medications and

defibrillation), after pacing:

dramatically improved ECG

showing ST elevations in leads

V1-V3 → later normal

NA Discontinuation of propofol,

transvenous pacer

Transoesophageal echocardiography: normal function, left ventricular

hypertrophy, mild pericardial effusion, no evidence of retrograde

dissection → an ejection fraction of 40%; coronary

angiogram: no abnormality

Survived

Jorens et al.68

2009

12 M Traumatic cerebral edema, epidural

hematoma

S NA NA 5 day

s

Rhabdomyolysis, arrhythmia

CK 863.000IU/L, elevated cardiac troponin levels, lactic acidosis, lipemic serum

with a triglyceride level of 591ng/ml

A sudden nodal bradyarrhythmia with coved-type

ST-segment elevation in the right precordial

leads → ventricular arrhythmias

Concomitant use of

catecholamines

Bicarbonate administration, dialysis, cardiac extracorporeal

support

Autopsy: an accumulation of fat droplets and acute

vacuolar degeneration and myocytolysis of skeletal

and cardiac muscle; massive reddish brown,

myoglobin-immunoreactivepigment casts in the renal tubular

lumina

Died

Weiner et al.69

2009

21 M Drug intoxication (alprazolam

S 25mcg/kg/

25mcg/kg/

˃14 hours

Arrthythmia Mixed acidosis (pH 7.14), potassium

RSR’ pattern with mild ST elevation

in V1-V2 → a

Concomitant use of dopamine


Coronary angiography: no obstructive coronary

disease; a cardiac

Survived

, tramadol) min min 5.4mEq/L, creatinine

2.34mg/dl, CPK 3.269 U/L,

troponin-I 2.82 ng/mL

pronounced Type I Brugada pattern

with coved type ST segment elevations

in V1-V2, anteroseptal leads → after stopping

propofol: resolution of the Brugada

pattern

magnetic resonance: normal LV and RV

function with no structural abnormalities

Roberts et al.70

2009

11 patients at the age

of: 58 ± 14

82% male

s, 18% females

Critically ill patients

S NA NA 5 (3-7)

Renal failure, (11 patients),

cardiac dysfunction (11 patients)

Metabolic acidosis (11

patients), hypertriglyceride

mia (1)

NA Catecholamines (10 patients)

NA NA 2 of the patients died

Da-Silva et al.71

2010

4 M Malignant status

epilepticus associated

with bacterial

meningitis

S 0.6-15.6

15.6 6 day

s

Dark green urine,

hypotension, rhabdomyolysis, arrhythmia

Metabolic acidosis (pH 7.32,

bicarbonates 15mEq/L), CK

155.400U/L, CK myoglobin

2.317ng/mL, troponin T 0.10µg/L,

triglycerides 5160mg/dL

Intermitent episodes of nonsinus

bradycardia → idioventricular vs.junctional

rhythm, increased QTc, and

ventricular escape → after transfusion and CVVH: sinus

rhythm

NA Discontinuation of propofol, treatment

by dopamine, calcium gluconate,

sodium bicarbonate; manual exchange transfusion with

600mL of packed red blood cells

(PRBCs) by using alternate push-pull

method (PECT: Parcial-exchange blood transfusion)

followed by CVVH

Echocardiography: normal shortening fractions of

38.9%, resp. 33.6%

Survived

Guitton et al.72

2010

17 F Refractory status

epilepticus, with

S NA 8.8 58 hours

Arterial hypotension, renal failure,

rhabdomyolysi

Metabolic acidosis ( pH 7.24, lactate 7.2mmol/L,

Bradycardia → prolonged QRS → normal QRS with sinus rhythm →

Because of hypotension norepinephri

ne

Fluid challenge and norepinephrine,

calcium gluconate, molar lactate

Chest X-ray: normal; Brain computed

tomography (with intravenous contrast):

Survived

aseptic meningoencephalitis

s, cardiocirculato

ry failure, arrhythmia

bicarbonate 12.2mmol/L), altered renal

function (potassium

5.3mmol/L, urea 13.7mg/dL, creatinine

2.7mg/dL),myoglobin˃30.000µg/L, CPK 168.000U/L,

increased troponin, AST

1.577U/L, ALT 245U/L

QRS waves gradually widened

→ cardiocirculator

y arrest with refractory ventricular

fibrillation → after ECMO: correction of

rhythmic conduction

infusions, bicarbonates, veno-

venous hemofiltration,

followed by extracorporeal

membrane oxygenation

(ECMO)

normal. Analysis of cerebrospinal fluid (CSF):raised protein (1.24 g/L), three leukocytes/mL, and

nobacteria (a diagnosis of

aseptic meningoencephalitis

suspected). echocardiography:

normal, without any changes in left ventricular

function → left ventricular function gradually decreased;

Abdominal and hepatic ultrasounds: normal; after

ECMO: progressive improvement of left ventricular function

Sammartino et al.73

2010

33 PCA preterm baby (born at 24-

week gestation)

NA Laser therapy for retinopathy

of prematurity

A Bolus of

3mg/kg +

infusion

: 60-80mg/kg/hou

r

80mg/kg/hou

r

2 hours

Hypotension, hyposaturation

Lipemic serum, AST 1.200UI/l, ALT 5.760UI/l,

cholesterol 102mg/dl,

triglycerides 2.168mg/dl, K

5.1mEq/l, blood urea nitrogen

33mg/dl

A decrease in heart rate ˂100bpm

NA Concomitant use of parenteral nutrition (suspended 3 hours

before surgery);Discontinuation of propofol, glucose

10% + NaCl + albumin, dopamine

NA Survived

Soler-Rodenas et

20 F Traumatic brain injury

S 2,6-6

6 5 day

Arrhythmia, rhabdomyolysi

Hyperkalemia, metabolic

Bradycardia → cardiac arrest

Catecholamines and steroids

Noradrenaline, adrenaline

NA Died

al.74 2010

s s, renal insufficience, hypotension,

cardiac failure

acidosis, phosphatemia 3,7

mmol/l, CK 36.204 U/l, myoglobin 590mg/l

Power et al.75

2011

NA

M Refractory status

epilepticus + viral

encephalitis

S 229,3

mg/h

NA 107, 5

hours

Cardiac arrhythmia, hypotension

and rhabdomyolysi

s

Respiratory and metabolic acidosis

Cardiac arrhythmia NA NA NA Died – PRIS cause of death?

Amrein et al.76

2011

20 M Traumatic head injury + bilateral

decompressive

craniectomy

S 4.5 mg/kg/h firstly + 1.4 mg/kg h secondly

4.5 Firstly: 6

days,

after

that reexposure for

procedur

e

Hypotension, rhabdomyolysis, arrhythmia

Serum creatine kinase 16.249

IU/L, no metabolic acidosis

Broad complex arrhythmia

Concomitant use of

norepinephrine

Aggressive fluid resuscitation

Computed tomography of the brain: bilateral brain

contusions and intracerebral hematoma;

Transesophageal echocardiogram: diffuse hypokinesia with a left

ventricular ejection fraction of 40%,

transthoracic echocardiogram:

normalization of left and right ventricular function

Survived

Diedrich et al.77

2011


S 1.8-8.4

8.4 ˃5 day

s

Rhabdomyolysis, fever,

hypotension, arrhythmia

Increased CK, myoglobin and

serum creatinine, metabolic acidosis

(2.4 mmol/L)

Tachycardia → bradycardia with a

RBBB → wide complex

tachycardia → ventricular

tachycardia, fibrillation →

asystole

NA Intravenous hydration,

phenylephrine, amiodarone, epinephrine,

atropine, calcium, sodium bicarbonate,

vasopressin

NA Died

47 F Astrocytoma

S 6-10.5

10.5 ˃8 day

s

Arrhythmia Increased creatinine kinase and triglycerides,

metabolic

Bradycardia with a RBBB → wide

complex pulseless electrical activity →

NA Phenylephrine; discontinuation of

propofol; intravenous calcium,

Transthoracic echocardiogram (TTE): generalized hypokinesis,

significant decrease in left

Died

acidosis, pH 7.25, bicarbonate 20mmol/L,

creatinine kinase 3538U/L

asystole glucagon; atropine, epinephrine, atrial

and ventricular pacing

ventricular function with an ejection fraction (EF)

of 30%,

Faulkner et al.78

2011


epilepticus (traumatic

brain injury and seizure disorder)

S 4,8 4,8 5 day

s

Acute renal failure, severe rhabdomyolysi

s

Lactic acidosis, hypertriglyceride

mia

A typicaltype I Brugada

pattern characterized

by up to 15 mm of high take-off

coved ST-segment

elevation in leads V1 and V2

→ the precordial STsegmentelevation

completely resolved

NA Discontinuation of propofol infusion,

aggressive hydration, plasma

exchange

Genetic testing negative for several

cardiac sodium-channel

and L-type calcium channel

abnormalities

Survived

Ramaiah et al.79

2011

42 F Parathyroidectomy, morbid obesity

(BMI 75), postoperati

ve respiratory

failure secondary to basal

atelectasis and

ventilator-associated

pneumonia, septic shock

secondary to urinary

tract infection

A+S Bolus

300 mg +

20-80 μg/kg/min

80 μg/kg/min (4

mg/kg/h

)

65 hours


rhabdomyolysis, oliguria,

Creatinine kinase (66900 IU/l) and

myoglobin (19470 ng/ml) levels

started to climb leading to the diagnosis of

rhabdomyolysis, increasing

creatinine (3.1 mg/dl) and BUN

(41 mg/dl), metabolic acidosis

with the base deficit of more

than 10 mmols/l

NA Norepinephrine Propofol infusion replaced with

titrating doses of lorazepam and

fentanyl for sedation,

hemodialysis

NA Died (cause of death other than PRIS)

and ventilator-associated pneumonia

Testerman et al.80

2011


S From 70 µg/kg/min up

NA ˃2 day

s

Hypotension, metabolic acidosis,

rhabdomyolysis, acute renal

failure, circulatory

collapse

Metabolic acidosis

NA NA Vasopressors, continuous venovenous hemodialysis

NA Died

40 M Head injury S 50-90 µg/kg/min

90 µg/kg/min

3 day

s


Bradyarrhythmia NA Stopping the propofol infusion,

supportive care measurements

NA Survived

Pisapia et al.81

2011

37 F Aneurysmal

subarachnoid

hemorrhage+ right

frontotemporal

craniotomy and

microsurgical

aneurysmclipping;

respiratory infection

S ˃4mg/kg/hou

r

80 mcg/kg/min (4.8 mg/kg/hour)

˃48 hours

Rhabdomyolysis, acute renal

failure, hypotension, arrhythmia

Metabolic (lactic) acidosis, CPK greater than ˃

29,000U/l, worsening

transaminitis, increased levels of cerebral LPR

Tachycardia, cardiac arrest

Catecholamine vassopressor use

Epinephrine, Norepinephrine,

Phenylepinephrine, Vasopressin

A head computedtomography (CT) scan:

subarachnoid hemorrhage, right frontal

intraparenchymalhemorrhage, and subdural

blood over the rightconvexity → a

postoperative head CT the following

day revealed infarction of the inferior right frontal,

temporal, and parietal lobes → an evolving

infarct in the distribution of

the right middle cerebral artery; A cerebral

angiogram: a 12-mm multilobulated aneurysm

arising from thesupraclinoid segment of the right internal carotid

artery; Microbiology:

Died

Staphylococcus aureus in respiratory culture

Vanlander et al.82

2012


(urgent trepanation

and postoperative care) +

Leberhereditary

optic neuropathy

(LHON)

S 4.8 mg/kg/h

5.35 mg/kg/h

88 hours

Hypotension, rhabdomyolysis, arrhythmia,

multiorgan failure,

refractory shock

Metabolic (lactic) acidosis, CK ˃

63711 IU/l,

Nodal bradyarrhythmia with coved ST-T segment elevation

in the right precordial leads and

atrioventricular dissociation

Noradrenalin Discontinuation of propofol infusion, renal replacement

therapy, supportive drugs (carnitine, thiamine, vitamin

B12) with the intention to support

mitochondrial function

Computed tomography: multiple hemorrhagic contusions in the left

frontoparietal region and an epidural hematoma in the right frontoparietal region → expanding lesions and edema;

Histology: congestion of the liver, the lower lobes

of the lungs and the brain, atrophy of the optic nerve, widespread myocytolysis in the diaphragm, skeletal and cardiac muscle, and massive accumulation of

fat in skeletal muscle fibers; Spectrophotometric

analysis of post-mortem skeletal muscle biopsy: a

severely deficient complex I activity, with significantly increased

activity of other OXPHOS complexes (II, III, IV) and

citrate synthase

Died

Annecke et al.83

2012

36 F Severe head injury – a severe bleeding from a

midfacial injury

S NA 2.8 mg/kg/h

7 day

s

Severe shock Elevated creatine kinase activity

1.800 U/L, metabolic (lactic)

acidosis, hyperkalemia 6.0

mmol/L, hyperphosphatemi

a 7.7 mg/dL, increased ALT and AST, GGT, normal bilirubin

Brugadasyndrome-like

electrocardiographic pattern → intermittent episodes of ventricular

tachycardia → bradyarrhythmia →

episodes of temporary pulsless electrical activity

Norepinephrine Dobutamine, norepinephrine, hemofiltration, epinephrine,

vasopressin, pacer wire introduction

Whole-body computed tomographic scan: an

open skull fracture with a small intraparenchymal hematoma of the right

temporal lobe,a traumatic subarachnoid hemorrhage, and multiple

complexfacial fractures; moderate

contusions of the leftlung, a non-dislocated pelvic fracture, and an

open fracture of

Died

the ankle joint also were noted; there was no

evidence ofcompartment syndromes → no hematoma growth

but moderate diffusebrain swelling, again with

no indication for neurosurgicalintervention

Richter et al.84

2012

39 M Catheter ablation of symptomati

c, drug-refractory

paroxysmal atrial

fibrillation

S during the

ablation procedur

e

NA 70 ml/h

<2 h

Arrhythmia No metabolic acidosis

Brugada pattern of coved-type > 2 mm ST-segment eleva-tion appeared in the

right precordial leads V1 and V2 →

after discontinuation of

propofol coved-type ST-segment

elevation gradually resolved and no

malignant ventric-ular arrhythmias

occurred → normal sinus rhythm

without any Bru-gada-like

repolarization abnormalities

NA Discontinuation of propofol infusion

To screen for drug-induced Brugada

syndrome, a class I AAD challenge (ajmaline 1

mg/kg over 5 min) was performed but failed to unmask a characteristic

coved-type Brugada electrocardiogram. Genetic testing was negative for known

cardiac sodium or calcium channel mutations related

to Brugada syndrome.

Survived

Annen et al.85

2012


S 7.3-12

12 49 hours

Fever, generalized

muscle weakness and

slow awakening, generalized

seizure, progressive cardiac and pulmonary

failure,

Metabolic (hyperchloremic)

acidosis (pH 7.19), ASAT ˃

20,000U/L, creatine kinase ˃

100,000 U/L, coagulopathy

(thrombin time ˃120 s,

prothrombin time 48%)

Supraventricular tachycardia (up to

180 bpm) → bradycardia →

asystole → resuscitation → bradyarrhytmia

resistant to therapy

Concomitant use of

norephinephrine, succinylcholine

Cessation of propofol infusion, mechanical and

medical resuscitation, renal

replacement therapy

CT brain scan: generalized edema of the brain with obliteration of

the basal cisterns and transtentorial herniation; Muscle biopsy: histology

revealed completely normal values, the muscle

could not be stimulated for in vitro muscle

contracture testing, but presented with

Died

peracute renal failure liver

failure, rhabdomyolysi

s

spontaneous muscle contracture; Blood

sample-molecular genetic investigations: no

mutation in the gene encoding for the skeletal muscle type 1 ryanodine receptor (RyR1), altered

intracellular calcium regulation via of

dysfunction of ryanodine receptors

Mijzen et al.86

2012

23 M Trauma brain

injury; a few

subcortical and pontine

high density lesions

suspected for diffuse

axonal injury (DAI)

S 4.7-5.8

5.8 7 day

s

Arrhythmia, circulatory

failure

Creatine kinase 246U/l, CKMB

36 U/l, HS-troponins 9ng/l,

metabolic (hyperchloremic)

acidosis (pH 7.28),

hyperlactataemia 3.8mmol/l,

hyperkalemia, hypertriglyceridemia 9,04 mmol/l, cardiac enzymes -

normal

Biphasic T-waves in the leads II, III and aVF → broad QST-complexes, ST depression in leads II, III, aVF and V4-V6 coved ST-elevations in

V1-V3 → refractory

circulatory failure

Concomitent use of

norepinephrine

Treatment with glucose and insulin

and calcium gluconate,

hemodialysis;

CT brain scan: diffuse brain swelling, a few

subcortical and pontine high density lesions suspected for diffuse axonal injury (DAI);

transthoracic echocardiography: normal left and right ventricular function; obduction: no

signs of widespread infection, no structural

abnormalities of the heart, and no cardial or hepatic histologic abnormalities

Died

Karaman et al.87

2013

5 F Neonatal adrenoleukodystrophy – operation of bilateral tenotomy, myotomy, bilateral

achilloplasty for the spasticity

A Bolus 2.5 mg/kg + 50

mcg/kg/min

NA 65 min

NA Hypertriglyceridemia 697mg/dl,

metabolic acidosis (pH 7.17),

hyperpotassemia 5.4, mEq/dl, high

levels of creatinine kinase

6640, CKMB 86.7, urea 12.8 mg/dl, SGOT

(serum glutamic oxaloacetic

transaminase) 199UI/l, and

ECG normal NA NA Echocardiography: normal; MRI: diffuse

density loss of periventricular white

matter; EEG: left hemisphere frontocentral

paroxysmal aktivity; Detection of high levels of

plasma very long-chain fatty acids (VLCFA) and

mutation in the PEX1 gene

Survived

SGPT (serum glutamic pyruvic transaminase) 74

UI//l, normal urine organic acid

analysis and normal tandem

mass results

Imam et al.88 2013

50 M Pneumothorax,

aspiration pneumonia, respiratory

distress

S 5.1 5.1 6 day

s

Subfebrile temperature, hypotension, bradycardia,

mild pulmonary

edema, acute kidney injury

Severe lactic acidosis,

leucocytosis 9550/uL, CK 51.000IU/L

Bradycardia → ventricular fibrillation

NA Treatment by norepinephrine and

dobutamine; intravenous fluids

A repeated chestradiograph: pneumothorax

and asmall zone of haziness on

the right lowerside suggesting aspiration

pneumonia

Died

Mayette et al.89

2013


S NA 9 mg/kg/h

2 day

s

Fluid resistant shock, acute

oliguric kidney failure,

arrhythmia

Severe metabolic acidosis, serumbicarbonate 10 mmol/L, lactate

11 mg/dL, a creatine kinase655,200 U/L,

whiteblood cells count

(WBC) 32 × 109/L, AST 3827

U/L,ALT 789 U/L,

alkaline phosphatase 193

U/L, total bilirubin

0.6 mg/dL, INR 1.4, hyperkalemia

8.8mmol/L, hypocalcemia

Right bundle branch block with left

anteriorfascicular block →unstable ventricular

tachycardia → sinus tachycardia with a persistent

right bundle branch block and septal

leadST-segment

depression →intraventricular

conductiondelays (IVCDs),

progressively widening QRS,

atrial flutter/fibrillation, and an

accelerated junctional escape

rhythm →ventricular

tachycardia →accelerated

NA Crystalloids, epinephrine treatment,

defibrillation, amiodarone, aggressive

calcium/magnesium replacement,

lidocaine, extracorporeal

membrane oxygenation, vasopressin, bicarbonate,

calcium chloride, bicarbonate,

insulin, glucose, sodium polystyrene

sulfonate, isoproterenol,

dopamine, transvenous pacing,

hemodialysis

NA Survived

junctional rhythm/ventricular

tachycardia →ventricular

fibrillation → ventricular

tachycardia →ventricular

fibrillation → asystole → paced rhythm → a sinus

rhythmwith minimal lateral

T-wave abnormalities

Agrawal et al.90

2013

53 F Trauma head injury, polytrauma (multiple fractures

with active bleeding in the pelvis,

liver lacerations with active bleeding), angiogram embolization of right hepatic arterial branch

and right internal

iliac artery for the

hepatic and pelvic

bleeding

S 1,2 –

5,7

5,7 5 day

s

Arrhythmia Metabolic acidosis (pH

7.03, lactate 11.5 mmol/L) and

hyperkalemia (K 9.3 mmol/L),

hypertriglyceridemia

Recurrent episodes of ventricular

Tachycardia → a cardiac arrest with

pulselesselectrical activity

Adrenaline 0.05–0.25

μg/kg/min (16 μg/250 ml

dextrose 5 %)

Resuscitation, adrenaline

boluses and insulin infusion

CT scanning: subarachnoidhemorrhages,

intraparenchymal contusions, right

humeral neck fracture, grade 3 liver lacerations

with activebleeding, comminuted

right superior and inferior pubic rami

fractures, right sacral ala fracture with active

bleeding in thepelvis; An exploratory

laparotomy: evidence of hypoperfused small

bowel,large bowel, stomach and liver with no evidence of

ischemiaor gangrene; liver

laceration was also noted with no signs ofactive bleeding.

Died

Schroeppel et al.91

2014


S NA NA NA Rhabdomyolysis, cardiac arrhythmias

NA Cardiac arrhythmias NA Stopping the propofol infusion

NA Survived

Linko et al.92 2014

19 M 45% TBSA flame burn

(smoke inhalation

injury suspicion)

A+S 1.96-

6.95

6.95 11 day

s

Hypotension, oliguria,

rhabdomyolysis, heart failure,

fever

Hyperlactataemia 6.1mmol/L,

increased plasma creatinine

concentration, serum troponin T

(TnT) concentration

Increased, plasma myoglobin

concentration increase to

1897 μg/L, no hypertermia, lactatemia,electrolyte disorders,

hypertriglyceridemia

ST-segment changes →a Brugada-

typeST-segment

elevation developed with a further

increase in plasma TnT concentration → Brugada-like ECG pattern → normalization

Norepinephrine infusion at a

dosageof 0.01

μg/kg/min to 0.1 μg/kg/min

.

Norepinephrine, fluid resuscitation,

sodium bicarbonate, renal replacement

therapy and cardiacsupport therapy, ontinuous veno-

venous hemodiafiltration,

levosimendan, hydrocortisone

(suspected sepsis),

Transthoracic echocardiography: an

extremely enlarged right side of

the heart with an increased pulmonary systolic

pressure, left ventricular function normal → a

normalfunction of the heart; A

muscle biopsy of the rightforearm: no signs of

myocitis orhereditary muscle

pathologies, but signs of postnecrotic regeneration,

typical forrhabdomyolysis; CT scan of the thorax: significant stress of the right side of

theheart without pulmonary

embolism. A focal musclecompartment syndrome of gluteal muscle was ruled

out, with incision of a gluteal region revealing

normalmuscle. A magnetic

resonance image (MRI): a pathologic, diffuse muscle

edema consistent withrhabdomyolysis. X-ray

scan of chest and mikrobiology: no pneumonia, sepsis

Survived

Poretti at al.93

3 F Sclerotherapy of large

A NA NA NA Acute renal failure,

Metabolic acidosis

NA NA NA MR: T2-hyperintensity and reduced diffusion

Survived

2014 venous malformati

on

rhabdomyolysis; transient

neurological deficits

(encephalopathy, weakness of arms and

legs)

within the supra- and infratentorial white matter

Diaz et al.94

201432 M Trauma,

postoperative

development of ARDS

S 50-125mcg

/kg/min

125mcg

/kg/min

8 day

s


rhabdomyolysis

Metabolic acidosis,

hypertriglyceridemia 2,370 mg/dL, hyperkalaemia 7.1 mmol/l, creatine

kinase 162,000U/L,

elevated hepatic transaminases, no

lipaemia

Cardiac arrest NA Norepinephrine, multiple

vasopressors, hemodialysis

Autopsy:acute bilateral pneumonia

with pulmonarycongestion and edema,

cardiomegaly (770 g) waspresent with concentric

left ventricular hypertrophy

(1.6 cm). The liver: evidence of chronicpassive congestion

without hepatomegaly or evidence

of fatty liver

Died

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http://www.ncbi.nlm.nih.gov/pubmed/?term=Karaman%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23302011

http://www.ncbi.nlm.nih.gov/pubmed/?term=Propofol+infusion+syndrome%3A+mijzen

http://www.ncbi.nlm.nih.gov/pubmed/?term=Rodgers%20MG%5BAuthor%5D&cauthor=true&cauthor_uid=22847396

http://www.ncbi.nlm.nih.gov/pubmed/?term=Aslan%20A%5BAuthor%5D&cauthor=true&cauthor_uid=22847396

http://www.ncbi.nlm.nih.gov/pubmed/?term=Jacobs%20B%5BAuthor%5D&cauthor=true&cauthor_uid=22847396

http://www.ncbi.nlm.nih.gov/pubmed/?term=Mijzen%20EJ%5BAuthor%5D&cauthor=true&cauthor_uid=22847396

http://www.ncbi.nlm.nih.gov/pubmed/?term=Propofol+infusion+syndrome%3A+annen

http://www.ncbi.nlm.nih.gov/pubmed/?term=Urwyler%20A%5BAuthor%5D&cauthor=true&cauthor_uid=24765478

http://www.ncbi.nlm.nih.gov/pubmed/?term=Girard%20T%5BAuthor%5D&cauthor=true&cauthor_uid=24765478

http://www.ncbi.nlm.nih.gov/pubmed/?term=Annen%20E%5BAuthor%5D&cauthor=true&cauthor_uid=24765478

http://www.ncbi.nlm.nih.gov/pubmed/?term=Propofol+infusion+syndrome%3A+richter

http://www.ncbi.nlm.nih.gov/pubmed/?term=Brugada%20P%5BAuthor%5D&cauthor=true&cauthor_uid=22302080

http://www.ncbi.nlm.nih.gov/pubmed/?term=Richter%20S%5BAuthor%5D&cauthor=true&cauthor_uid=22302080

http://www.ncbi.nlm.nih.gov/pubmed/?term=Propofol+infusion+syndrome%3A+annecke

http://www.ncbi.nlm.nih.gov/pubmed/?term=Propofol+infusion+syndrome%3A+annecke

http://www.ncbi.nlm.nih.gov/pubmed/?term=Ney%20L%5BAuthor%5D&cauthor=true&cauthor_uid=22284319

http://www.ncbi.nlm.nih.gov/pubmed/?term=Conzen%20P%5BAuthor%5D&cauthor=true&cauthor_uid=22284319

http://www.ncbi.nlm.nih.gov/pubmed/?term=Annecke%20T%5BAuthor%5D&cauthor=true&cauthor_uid=22284319

Part S2: Step-by-step multiple logistic regressionLast change: 7.5.2015Statistician: P. WaldaufSoftware: Stata 14

Content of Part S2

Part S2: Step-by-step multiple logistic regression................................................................................................................................................................................................. 56

Descriptive statistics + univariant mortality analysis............................................................................................................................................................................................. 59

Mortality........................................................................................................................................................................................................................................................... 59

Age.................................................................................................................................................................................................................................................................... 59

Child.................................................................................................................................................................................................................................................................. 65

Sex..................................................................................................................................................................................................................................................................... 66

Underlying dg.................................................................................................................................................................................................................................................... 67

Resp.infection................................................................................................................................................................................................................................................ 67

TBI................................................................................................................................................................................................................................................................. 68

Status epilepticus.......................................................................................................................................................................................................................................... 69

Non-trauma neurological dg.......................................................................................................................................................................................................................... 70

Other............................................................................................................................................................................................................................................................. 71

Average infusion rate........................................................................................................................................................................................................................................ 72

Duration............................................................................................................................................................................................................................................................ 78

Cumulative dose mg/kg..................................................................................................................................................................................................................................... 83

Symtoms............................................................................................................................................................................................................................................................ 89

Arrhythmia.................................................................................................................................................................................................................................................... 90

Cardiac failure............................................................................................................................................................................................................................................... 90

Metabolic acidosis......................................................................................................................................................................................................................................... 91

Lipaemia or elevated triacylglyceroles (TAG)................................................................................................................................................................................................ 92

Hyperkalemia................................................................................................................................................................................................................................................ 93

Derranged liver function tests....................................................................................................................................................................................................................... 94

Rhabdomyolysis (myo, ^CK).......................................................................................................................................................................................................................... 95

AKI (anuria, oliguria, ^creatinine).................................................................................................................................................................................................................. 96

Discoloration of urine.................................................................................................................................................................................................................................... 97

Hepatomegaly or fatty infiltration of liver..................................................................................................................................................................................................... 98

Pulmonary oedema....................................................................................................................................................................................................................................... 99

Fever............................................................................................................................................................................................................................................................ 100

Hypotension................................................................................................................................................................................................................................................ 101

ECG changes................................................................................................................................................................................................................................................ 102

Multivariant analysis........................................................................................................................................................................................................................................... 103

Missing values analysis.................................................................................................................................................................................................................................... 103

Correlation analysis......................................................................................................................................................................................................................................... 104

Symptoms.................................................................................................................................................................................................................................................... 104

Model 1........................................................................................................................................................................................................................................................... 107

Additional calculations........................................................................................................................................................................................................................................ 109

Fever and cummulative dose.......................................................................................................................................................................................................................... 109

Fever and average infusion rate...................................................................................................................................................................................................................... 111

Descriptive statistics + univariant mortality analysisMortalitytab Mortality

Total 152 100.00 died 78 51.32 100.00 survived 74 48.68 48.68 Mortality Freq. Percent Cum.

Mortalita in the whole data set is 51,32%

Agetabstat Age , stat( N mean sd median q min max)

Age 148 29.3027 20.38796 27 12 27 45.5 .02 71 variable N mean sd p50 p25 p50 p75 min max

graph box Agehistogram Age

020

4060

80A

ge0

0.0

1.0

2.0

3D

ensi

ty

0 20 40 60 80Age0

Relation to mortality:tabstat Age , by( Mortality ) stat( N mean sd median q min max)

Total 148 29.3027 20.38796 27 12 27 45.5 .02 71 died 74 25.45027 17.35156 23.5 10 23.5 39 .08 64 survived 74 33.15514 22.49147 33 13 33 57 .02 71 Mortality N mean sd p50 p25 p50 p75 min max

by categories of: Mortality (Mortality)Summary for variables: Age

graph box Age, by(Mortality)

020

4060

80

survived died

Age

0

Graphs by Mortality

regress Age i.Mortality

_cons 33.15514 2.33502 14.20 0.000 28.54033 37.76994 died -7.704865 3.302217 -2.33 0.021 -14.23119 -1.178543 Mortality Age Coef. Std. Err. t P>|t| [95% Conf. Interval]

Total 61103.3483 147 415.669036 Root MSE = 20.087 Adj R-squared = 0.0293 Residual 58906.8454 146 403.471544 R-squared = 0.0359 Model 2196.50288 1 2196.50288 Prob > F = 0.0210 F( 1, 146) = 5.44 Source SS df MS Number of obs = 148

Pacienti who died are on average by 7.7 years younger (p=0,021). Now we divide patients into subgroups according to age and compare mortality among these groups. .

Patients divided into 5 pentiles of age:xtile Age_pentiles= Age , nq(5)tabstat Age , by( Age_pentiles ) stat( N mean sd median q min max)

Total 148 29.3027 20.38796 27 12 27 45.5 .02 71 5 29 59.24138 3.897391 58 57 58 58 55 71 4 28 43.03571 4.598568 41.5 39 41.5 46.5 38 53 3 30 28.63333 5.486556 28.5 24 28.5 33 21 37 2 30 15.56667 3.701662 17 13 17 18 8 20 1 31 2.832258 2.363875 2 .75 2 5 .02 7 Age_pentiles N mean sd p50 p25 p50 p75 min max

by categories of: Age_pentiles (5 quantiles of Age )Summary for variables: Age

tab Age_pentiles Mortality, row

50.00 50.00 100.00 Total 74 74 148 86.21 13.79 100.00 5 25 4 29 35.71 64.29 100.00 4 10 18 28 36.67 63.33 100.00 3 11 19 30 40.00 60.00 100.00 2 12 18 30 51.61 48.39 100.00 1 16 15 31 of Age survived died Total quantiles Mortality 5

row percentage frequency Key

Table shows that the lowest mortality (13.8%) is in the 5th age pentile (55-71 yr). In other age groups (0.2-53 yr) is mortality very uniform around 60%. logistic Mortality i.Age_pentiles

_cons .9375 .3369353 -0.18 0.857 .4635018 1.89623 5 .1706667 .1104949 -2.73 0.006 .0479794 .6070757 4 1.92 1.0245 1.22 0.222 .6746918 5.463828 3 1.842424 .9621395 1.17 0.242 .6620341 5.12742 2 1.6 .8283853 0.91 0.364 .5799869 4.413893Age_pentiles Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]

Log likelihood = -91.260203 Pseudo R2 = 0.1104 Prob > chi2 = 0.0001 LR chi2(4) = 22.65Logistic regression Number of obs = 148

pwcompare Age_pentiles , effects

5 vs 4 -2.420368 .6674995 -3.63 0.000 -3.728643 -1.112093 5 vs 3 -2.379125 .6584381 -3.61 0.000 -3.66964 -1.08861 4 vs 3 .041243 .5468969 0.08 0.940 -1.030655 1.113141 5 vs 2 -2.238047 .6548961 -3.42 0.001 -3.521619 -.9544738 4 vs 2 .1823216 .5426274 0.34 0.737 -.8812085 1.245852 3 vs 2 .1410786 .531441 0.27 0.791 -.9005267 1.182684 5 vs 1 -1.768043 .6474308 -2.73 0.006 -3.036984 -.4991019 4 vs 1 .6523252 .5335937 1.22 0.222 -.3934992 1.69815 3 vs 1 .6110822 .5222139 1.17 0.242 -.4124382 1.634603 2 vs 1 .4700036 .5177408 0.91 0.364 -.5447497 1.484757Age_pentiles Mortality Contrast Std. Err. z P>|z| [95% Conf. Interval] Unadjusted Unadjusted

Margins : asbalanced

Pairwise comparisons of marginal linear predictions

logistic Mortality i.Age_pentilesmargins Age_pentilesmarginsplot, xdimension( Age_pentiles ) xscale(range(0.5 3.5)) title("MORTALITY") legend(off) ytitle("") xtitle(Age pentiles[years])

0.2

.4.6

.8

0.2-7 8-20 21-37 38-53 55-71Age pentiles[years]

MORTALITY

I create a Binary parametr AgeBelow55 (coding: 55+ years = 0, <55 years = 1)recode Age_pentiles (5 = 0) (1 = 1) (2=1) (3=1) (4=1), gen(AgeBelow55)tab Age_pentiles AgeBelow55logistic Mortality i.AgeBelow55

_cons .16 .0861626 -3.40 0.001 .0556844 .45973341.AgeBelow55 8.928571 5.087671 3.84 0.000 2.922476 27.27803 Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Pacients <55 years have higher mortality OR 8.9 p<0,001,logistic regression.

Childtab Child

Total 151 100.00 yes 55 36.42 100.00 no 96 63.58 63.58 Child Freq. Percent Cum.

The group contains 36,4% children <18 years

Relation to mortality:tab Child Mortality, row

49.01 50.99 100.00 Total 74 77 151 43.64 56.36 100.00 yes 24 31 55 52.08 47.92 100.00 no 50 46 96 Child survived died Total Mortality


Mortality of children is 56% and of adults 48% which is not significantly different (logistic regression p=0,318).logistic Mortality i.Child

_cons .92 .1879574 -0.41 0.683 .6164332 1.37306 yes 1.403986 .4774869 1.00 0.318 .7208986 2.734331 Child Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Lastly I explore whether small children (<2 yrs) differ in mortality.gen AgeBelow2 =.replace AgeBelow2 = 1 if Age < 2

tab AgeBelow2 Mortality, row

50.00 50.00 100.00 Total 7 7 14 50.00 50.00 100.00 1 7 7 14 AgeBelow2 survived died Total Mortality


There are 14 babies in the dataset and their mortality is 50%.

Sextab Male

Total 133 100.00 male 80 60.15 100.00 female 53 39.85 39.85 Sex Freq. Percent Cum.

logistic Male

_cons 1.509434 .2673357 2.32 0.020 1.066738 2.135848 Male Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]

Log likelihood = -89.428832 Pseudo R2 = 0.0000 Prob > chi2 = . LR chi2(0) = 0.00Logistic regression Number of obs = 133

There is 60,2% of female patients in the dataset. Of note, sex is not known for 19 patients.

Relation to mortality:tab Male Mortality, row

53.38 46.62 100.00 Total 71 62 133 55.00 45.00 100.00 male 44 36 80 50.94 49.06 100.00 female 27 26 53 Sex survived died Total Mortality


logistic Mortality i.Male

_cons .962963 .2645934 -0.14 0.891 .5619852 1.650039 male .8496504 .3016003 -0.46 0.646 .4237301 1.703692 Male Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


There is no difference in mortality between female (49%) and male (45%) patients – (logistic regression p=0,646).

Underlying dgResp.infectiontab Resp_infection

Total 152 100.00 yes 22 14.47 100.00 no 130 85.53 85.53 ion Freq. Percent Cum.Resp.infect

14,5% pacients had respirátory infection.

Relation to mortality:tab Resp_infection Mortality, row

48.68 51.32 100.00 Total 74 78 152 31.82 68.18 100.00 yes 7 15 22 51.54 48.46 100.00 no 67 63 130 tion survived died TotalResp.infec Mortality


logistic Mortality i.Resp_infection

_cons .9402985 .1650174 -0.35 0.726 .6666293 1.326316 yes 2.278912 1.117183 1.68 0.093 .871858 5.956747Resp_infection Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Mortality of patients with Resp Inf is 68.2%, as compared to 48.5% in patients without respirátory infection , OR 2.3 p=0.093 TBItab TBI

Total 152 100.00 yes 43 28.29 100.00 no 109 71.71 71.71 TBI Freq. Percent Cum.

There are 28.3% of patients with TBI.

Relations to mortality:tab TBI Mortality, row

48.68 51.32 100.00 Total 74 78 152 23.26 76.74 100.00 yes 10 33 43 58.72 41.28 100.00 no 64 45 109 TBI survived died Total Mortality


logistic Mortality i.TBI

_cons .703125 .1367885 -1.81 0.070 .4802161 1.029505 yes 4.693333 1.924554 3.77 0.000 2.101051 10.48398 TBI Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Pacients with TBI have mortality of 76.7% and without TBI 41.3%, OR 4,7 p< 0,001 (logistic regression).

Status epilepticustab Status_epilepticus tab Status_epilepticustab Status_epilepticus

Total 152 100.00 yes 30 19.74 100.00 no 122 80.26 80.26 epilepticus Freq. Percent Cum. Status

There are 19.7% of patients with status epilepticus .

Relations to mortality:tab Status_epilepticus Mortality, row

48.68 51.32 100.00 Total 74 78 152 56.67 43.33 100.00 yes 17 13 30 46.72 53.28 100.00 no 57 65 122 s survived died Totalepilepticu Mortality Status


logistic Mortality i.Status_epilepticus

_cons 1.140351 .2069304 0.72 0.469 .7990569 1.627419 yes .6705883 .2754111 -0.97 0.331 .2998244 1.49984Status_epilepticus Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Pacients with SE have mortality of 43.3% as compared to 53.3% in patients without SE (p=0.331, logistic regression).

Non-trauma neurological dg.tab Nontrauma_neuro_dg

Total 152 100.00 yes 15 9.87 100.00 no 137 90.13 90.13 l dg. Freq. Percent Cum.neurologica Non-trauma

There are 9.9% of patients with non-traumatic non-epileptic neurological dg.

Relations to mortality:tab Nontrauma_neuro_dg Mortality, row

48.68 51.32 100.00 Total 74 78 152 60.00 40.00 100.00 yes 9 6 15 47.45 52.55 100.00 no 65 72 137 al dg. survived died Totalneurologic MortalityNon-trauma


logistic Mortality i.Nontrauma_neuro_dg

_cons 1.107692 .1895206 0.60 0.550 .7921051 1.549014 yes .6018519 .3334994 -0.92 0.360 .2031515 1.783032Nontrauma_neuro_dg Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Patients with non-traumatic neurological dg. Have mortality of 40% as compared to 52.6% , p=0.36 (logistic regression)

Otherreplace Other = 0 if Other ==.tab Other

Total 153 100.00 yes 43 28.10 100.00 no 110 71.90 71.90 Other Freq. Percent Cum.

There are 28.1% of patients with other diagnoses.

Relation to mortality:tab Other Mortality, row

48.68 51.32 100.00 Total 74 78 152 72.09 27.91 100.00 yes 31 12 43 39.45 60.55 100.00 no 43 66 109 Other survived died Total Mortality


logistic Mortality i.Other

_cons 1.534884 .3008033 2.19 0.029 1.045343 2.253679 yes .2521995 .0989698 -3.51 0.000 .1168719 .5442248 Other Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Pacients with Other diagnoses have mortality of 27.9% as compared to 60.6% in the restof the data set, p<0,001 OR 0,25, logistic regression.

Average infusion ratetabstat Average_dose , stat( N mean sd median q min max)

Average_dose 128 6.245938 2.833732 5.8 4 5.8 7.78 1.5 15.2 variable N mean sd p50 p25 p50 p75 min max

Missing data in 153-128 = 25 pacientsgraph box Average_dose

05

1015

Ave

rage

dos

e (m

g/kg

.h)

Relation to mortality:tabstat Average_dose, by( Mortality ) stat( N mean sd median q min max)

Total 128 6.245938 2.833732 5.8 4 5.8 7.78 1.5 15.2 died 68 6.662647 2.578686 6 5.05 6 7.78 1.9 15.2 survived 60 5.773667 3.0507 5 3.42 5 7.75 1.5 15 Mortality N mean sd p50 p25 p50 p75 min max

graph box Average_dose, by(Mortality)

05

1015

survived died

Ave

rage

dos

e (m

g/kg

.h)

Graphs by Mortality

regress Average_dose i.Mortality

_cons 5.773667 .3627176 15.92 0.000 5.055859 6.491474 died .8889804 .4976445 1.79 0.076 -.0958433 1.873804 Mortality Average_dose Coef. Std. Err. t P>|t| [95% Conf. Interval]


Nonsurvivors recieved on average 6.7 mg/kg/h as compared to 5.8 mg/kg/h in survivors, p=0,076, linear regression.logistic Mortality c.Average_dose

_cons .5504316 .2453547 -1.34 0.180 .2297632 1.31864Average_dose 1.12367 .0748874 1.75 0.080 .9860757 1.280464 Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Now I divide patients into pentils and xtile Average_dose_pentiles= Average_dose, nq(5)tabstat Average_dose, by(Average_dose_pentiles ) stat( N mean sd median q min max)

Total 128 6.245938 2.833732 5.8 4 5.8 7.78 1.5 15.2 5 25 10.7728 2.117112 10 9.4 10 12 8.1 15.2 4 25 7.3264 .5667957 7.4 6.9 7.4 8 6.1 8 3 26 5.753846 .3062427 5.9 5.5 5.9 6 5.1 6 2 18 4.787778 .2980043 4.99 4.5 4.99 5 4.1 5 1 34 3.271176 .645266 3.42 3 3.42 4 1.5 4 Average_dose_pentiles N mean sd p50 p25 p50 p75 min max

by categories of: Average_dose_pentiles (5 quantiles of Average_dose)Summary for variables: Average_dose

tab Average_dose_pentiles Mortality, row

.

46.88 53.13 100.00 Total 60 68 128 48.00 52.00 100.00 5 12 13 25 24.00 76.00 100.00 4 6 19 25 26.92 73.08 100.00 3 7 19 26 61.11 38.89 100.00 2 11 7 18 70.59 29.41 100.00 1 24 10 34 se survived died TotalAverage_do Mortality of quantiles 5


logistic Mortality i. Average_dose_pentilesmargins Average_dose_pentilesmarginsplot, xdimension( Average_dose_pentiles ) xscale(range(0.5 3.5)) title("MORTALITY") legend(off) ytitle("") xtitle(Average dose pentiles[mg/kg/hr])

.2.4

.6.8

1

1.5-4 4.1-5 5.1-6 6.1-8 8.1-15.2Average dose pentiles[mg/kg/hr]

MORTALITY

pwcompare Average_dose_pentiles , effects

5 vs 4 -1.072637 .6160801 -1.74 0.082 -2.280132 .134858 5 vs 3 -.9184861 .5964437 -1.54 0.124 -2.087494 .2505221 4 vs 3 .1541507 .6440396 0.24 0.811 -1.108144 1.416445 5 vs 2 .5320278 .6277122 0.85 0.397 -.6982656 1.762321 4 vs 2 1.604665 .6731006 2.38 0.017 .2854116 2.923918 3 vs 2 1.450514 .6551755 2.21 0.027 .1663935 2.734634 5 vs 1 .9555112 .5494753 1.74 0.082 -.1214405 2.032463 4 vs 1 2.028148 .6008035 3.38 0.001 .8505947 3.205701 3 vs 1 1.873997 .5806508 3.23 0.001 .7359426 3.012052 2 vs 1 .4234834 .6127258 0.69 0.489 -.7774371 1.624404Average_dose_pentiles Mortality Contrast Std. Err. z P>|z| [95% Conf. Interval] Unadjusted Unadjusted



logistic Mortality c.Average_dose

_cons .5504316 .2453547 -1.34 0.180 .2297632 1.31864Average_dose 1.12367 .0748874 1.75 0.080 .9860757 1.280464 Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


margins, at (Average_dose =( 1(1) 15))marginsplot, recastci(rarea) ci1opts(fintensity(20) lwidth(vvthin))

.2.4

.6.8

1P

r(M

orta

lity)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15Average dose (mg/kg.h)

Adjusted Predictions with 95% CIs

Now I create categorial parameter Average_dose_above5, identifiying patients with PRIS induced by the dose abowe the maximum allowed propofol dose. I will merge pentils 1 and 2 (Group 0) and pentiles 3, 4 and 5 (Group 1)recode Average_dose_pentiles (1 = 0) (2=0) (3=1) (4=1) (5 = 1), gen(Average_dose_above5)logistic Mortality i.Average_dose_above5

_cons .4857143 .14359 -2.44 0.015 .2721092 .86699881.Average_dose_above5 4.2 1.61032 3.74 0.000 1.981028 8.904468 Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Pacients in Group 1 have higher mortality than Group 0 – OR 4,2, p<0,001

Durationtabstat Duration , stat( N mean sd median q min max)

Duration 150 73.60293 50.64773 72 44 72 96 .66 264 variable N mean sd p50 p25 p50 p75 min max

graph box Duration

050

100

150

200

250

Dur

atio

n [h

]

Relations to mortaliny:tabstat Duration , by( Mortality ) stat( N mean sd median q min max)

Total 150 73.60293 50.64773 72 44 72 96 .66 264 died 78 80.00641 41.03455 72 58 72 104 4 192 survived 72 66.66583 58.84992 72 6.75 72 94 .66 264 Mortality N mean sd p50 p25 p50 p75 min max

by categories of: Mortality (Mortality)Summary for variables: Duration

graph box Duration , by(Mortality)

050

100

150

200

250

survived diedD

urat

ion

[h]

Graphs by Mortality

regress Duration i.Mortality

_cons 66.66583 5.93659 11.23 0.000 54.9344 78.39726 died 13.34058 8.232569 1.62 0.107 -2.927988 29.60914 Mortality Duration Coef. Std. Err. t P>|t| [95% Conf. Interval]


There is a trend to longer duration in nonsurvivors (mean 80 hours) as compared to survivors (mean 67 hours), p=0,107 linear regression.Now I divide patients into pentils according to infusion duration and compare mortality among them. xtile Duration_pentiles= Duration, nq(5)tabstat Duration, by(Duration_pentiles ) stat( N mean sd median q min max)

Total 150 73.60293 50.64773 72 44 72 96 .66 264 5 30 148.7667 35.01003 144 120 144 168 115 264 4 30 95.61667 4.490763 96 92 96 96 89 107.5 3 25 71.628 6.787336 72 66 72 72 60 88 2 35 49.38571 11.00139 55 48 55 58 23 58 1 30 6.324667 3.814942 5 5 5 8 .66 15 Duration_pentiles N mean sd p50 p25 p50 p75 min max

by categories of: Duration_pentiles (5 quantiles of Duration)Summary for variables: Duration

tab Duration_pentiles Mortality, row

48.00 52.00 100.00 Total 72 78 150 43.33 56.67 100.00 5 13 17 30 56.67 43.33 100.00 4 17 13 30 36.00 64.00 100.00 3 9 16 25 17.14 82.86 100.00 2 6 29 35 90.00 10.00 100.00 1 27 3 30 Duration survived died Total of Mortality quantiles 5


logistic Mortality i. Duration_pentilesmargins Duration_pentilesmarginsplot, xdimension( Duration_pentiles ) xscale(range(0.5 3.5)) title("MORTALITY") legend(off) ytitle("") xtitle(Duration pentiles[hrs])

0.2

.4.6

.81

1 2 3 4 5Duration pentiles[hrs]

MORTALITY

pwcompare Duration_pentiles , effects

5 vs 4 .536528 .5210501 1.03 0.303 -.4847115 1.557767 5 vs 3 -.3071002 .5561994 -0.55 0.581 -1.397231 .7830305 4 vs 3 -.8436281 .5561994 -1.52 0.129 -1.933759 .2465026 5 vs 2 -1.307272 .5804275 -2.25 0.024 -2.444889 -.1696555 4 vs 2 -1.8438 .5804275 -3.18 0.001 -2.981417 -.7061834 3 vs 2 -1.000172 .6121769 -1.63 0.102 -2.200017 .1996724 5 vs 1 2.465489 .711419 3.47 0.001 1.071133 3.859844 4 vs 1 1.928961 .711419 2.71 0.007 .534605 3.323316 3 vs 1 2.772589 .737551 3.76 0.000 1.327015 4.218162 2 vs 1 3.772761 .7559893 4.99 0.000 2.291049 5.254473Duration_pentiles Mortality Contrast Std. Err. z P>|z| [95% Conf. Interval] Unadjusted Unadjusted



tyto kategorie se dají spojit: 3+4+5

There is similar mortality in 3rd, 4th and 5th pentils and they can be merged into 1 category (Duration above 60 hours)

recode Duration_pentiles (1 = 1) (2=2) (3=3) (4=3) (5 = 3), gen(Duration_3)tabstat Duration, by( Duration_3 ) stat( N mean sd median q min max)

Total 150 73.60293 50.64773 72 44 72 96 .66 264 3 85 107.32 38.53379 96 76 96 120 60 264 2 35 49.38571 11.00139 55 48 55 58 23 58 1 30 6.324667 3.814942 5 5 5 8 .66 15 Duration_3 N mean sd p50 p25 p50 p75 min max

by categories of: Duration_3 (RECODE of Duration_pentiles (5 quantiles of Duration))Summary for variables: Duration

Now we have 3 categories of duration of propofol infusion: <20 hours, 20 -60hours and above 60 hours logistic Mortality i.Duration_3

_cons .4857143 .14359 -2.44 0.015 .2721092 .86699881.Average_dose_above5 4.2 1.61032 3.74 0.000 1.981028 8.904468 Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


logistic Mortality i.Duration_3

_cons .1111111 .0676201 -3.61 0.000 .033708 .3662539 3 10.61538 6.861108 3.65 0.000 2.990703 37.67889 2 43.5 32.88553 4.99 0.000 9.885304 191.4205 Duration_3 Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


pwcompare Duration_3 , or effects

3 vs 2 .2440318 .1216566 -2.83 0.005 .0918542 .6483265 3 vs 1 10.61538 6.861108 3.65 0.000 2.990703 37.67889 2 vs 1 43.5 32.88553 4.99 0.000 9.885304 191.4205 Duration_3 Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval] Unadjusted Unadjusted



As compared to patients with infusion duration <20 min, pacienti with duration of infusion 20-60 min have higher mortality O(R 43.5, p<0,001) as well as patients with the duration above 60 hours (OR 10.6, p<0,001)

Cumulative dose mg/kgtabstat Cum_dose , stat( N mean sd median q min max)

Cum_dose 128 490.2887 351.7994 423.4 314.64 423.4 612 3.24 1918.08 variable N mean sd p50 p25 p50 p75 min max

Missing data 152-128 = 24 pacients. graph box Cum_dose

050

01,

000

1,50

02,

000

Cum

dos

e m

g/kg

vztah k mortalitě:tabstat Cum_dose, by( Mortality ) stat( N mean sd median q min max)

Total 128 490.2887 351.7994 423.4 314.64 423.4 612 3.24 1918.08 died 68 542.4309 302.8553 432 336.4 432 681.85 28 1536 survived 60 431.1943 394.4131 316.92 112.5 316.92 596 3.24 1918.08 Mortality N mean sd p50 p25 p50 p75 min max

graph box Cum_dose , by(Mortality)

050

01,

000

1,50

02,

000

survived diedC

um d

ose

mg/

kg

Graphs by Mortality

regress Cum_dose i.Mortality

_cons 431.1943 45.02126 9.58 0.000 342.0985 520.29 died 111.2366 61.76866 1.80 0.074 -11.00175 233.475 Mortality Cum_dose Coef. Std. Err. t P>|t| [95% Conf. Interval]

Total 15717879.1 127 123762.827 Root MSE = 348.73 Adj R-squared = 0.0174 Residual 15323471 126 121614.85 R-squared = 0.0251 Model 394408.011 1 394408.011 Prob > F = 0.0741 F( 1, 126) = 3.24 Source SS df MS Number of obs = 128

Nonsurvivors were exposed to cummulative dose by 111 mg/kg higher than survivors . p=0,074. Now mortality will be compared in pentiles according to cummulative dose.

xtile Cum_dose_pentiles= Cum_dose, nq(5)tabstat Cum_dose , by( Cum_dose_pentiles ) stat( N mean sd median q min max)

Total 128 490.2887 351.7994 423.4 314.64 423.4 612 3.24 1918.08 5 24 1070.303 307.8061 960 852.45 960 1296 721.89 1918.08 4 27 579.3889 74.17405 576 499.2 576 643.7 480 720 3 25 421.184 23.17103 423.4 415.8 423.4 432 374.4 464 2 23 323.6496 12.54275 319 314.64 319 330.6 314.64 357.2 1 29 119.0568 109.6049 45 27 45 216 3.24 288 Cum_dose_pentiles N mean sd p50 p25 p50 p75 min max

by categories of: Cum_dose_pentiles (5 quantiles of Cum_dose)Summary for variables: Cum_dose

tab Cum_dose_pentiles Mortality, row

.

46.88 53.13 100.00 Total 60 68 128 33.33 66.67 100.00 5 8 16 24 48.15 51.85 100.00 4 13 14 27 28.00 72.00 100.00 3 7 18 25 56.52 43.48 100.00 2 13 10 23 65.52 34.48 100.00 1 19 10 29 Cum_dose survived died Total of Mortality quantiles 5


logistic Mortality i.Cum_dose_pentiles

_cons .5263158 .2056215 -1.64 0.100 .2447362 1.131865 5 3.8 2.21619 2.29 0.022 1.211591 11.91821 4 2.046154 1.12256 1.31 0.192 .6981562 5.996861 3 4.885714 2.894736 2.68 0.007 1.529677 15.60473 2 1.461538 .8390232 0.66 0.509 .4744192 4.502547Cum_dose_pentiles Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


pwcompare Cum_dose_pentiles , effects

5 vs 4 .6190392 .5795271 1.07 0.285 -.516813 1.754891 5 vs 3 -.2513143 .6212187 -0.40 0.686 -1.468881 .966252 4 vs 3 -.8703535 .588867 -1.48 0.139 -2.024512 .2838046 5 vs 2 .9555114 .6036746 1.58 0.113 -.2276691 2.138692 4 vs 2 .3364722 .5703286 0.59 0.555 -.7813513 1.454296 3 vs 2 1.206826 .6126465 1.97 0.049 .0060606 2.407591 5 vs 1 1.335001 .583208 2.29 0.022 .1919344 2.478068 4 vs 1 .7159619 .5486194 1.31 0.192 -.3593124 1.791236 3 vs 1 1.586315 .5924899 2.68 0.007 .4250565 2.747574 2 vs 1 .3794896 .5740685 0.66 0.509 -.745664 1.504643Cum_dose_pentiles Mortality Contrast Std. Err. z P>|z| [95% Conf. Interval] Unadjusted Unadjusted



logistic Mortality i.Cum_dose_pentilesmarginsplot, xdimension( Cum_dose_pentiles ) xscale(range(0.5 3.5)) title("MORTALITY") legend(off) ytitle("") xtitle(Cum dose[mg/kg])

.2.4

.6.8

1

3-288 315-357 374-464 480-720 722-1918Cum dose[mg/kg]

MORTALITY

logistic Mortality Cum_dose

_cons .7127308 .2243892 -1.08 0.282 .38454 1.32102 Cum_dose 1.000961 .0005479 1.75 0.079 .9998877 1.002035 Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


margins, at (Cum_dose=( 0(200) 2000))marginsplot, recastci(rarea) ci1opts(fintensity(20) lwidth(vvthin)) ci2opts(fintensity(20) lwidth(vvthin))marginsplot, recastci(rarea) ci1opts(fintensity(20) lwidth(vvthin))

Pentiles 1-2 and 3-4-5 can be merged into 2 categories (Cummulative dose above or below 360 mg/kg)

.2.4

.6.8

1P

r(M

orta

lity)

0 200 400 600 800 1000 1200 1400 1600 1800 2000Cum dose mg/kg

Adjusted Predictions with 95% CIs

recode Cum_dose_pentiles (1 = 0) (2=0) (3=1) (4=1) (5=1), gen(Cum_dose_above360)tabstat Cum_dose , by( Cum_dose_above360 ) stat( N mean sd median q min max)

Total 128 490.2887 351.7994 423.4 314.64 423.4 612 3.24 1918.08 1 76 682.3733 325.344 576 432 576 826.2 374.4 1918.08 0 52 209.5497 131.1146 288 32.25 288 314.64 3.24 357.2 Cum_dose_above360 N mean sd p50 p25 p50 p75 min max

by categories of: Cum_dose_above360 (RECODE of Cum_dose_pentiles (5 quantiles of Cum_dose))Summary for variables: Cum_dose

logistic Mortality i.Cum_dose_above360

_cons .625 .1781524 -1.65 0.099 .3574788 1.0927221.Cum_dose_above360 2.742857 1.018179 2.72 0.007 1.325036 5.67778 Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Pacients exposed to cummulative dose above 360 mg/kg have higher mortality: OR 2.74, p=0.007

SymtomsArrhythmiatab Arrhythmia

Total 152 100.00 yes 101 66.45 100.00 no 51 33.55 33.55 Arrhythmia Freq. Percent Cum.

66.5% pacients had arrhytmia

Relation to mortality:tab Arrhythmia Mortality, row

48.68 51.32 100.00 Total 74 78 152 36.63 63.37 100.00 yes 37 64 101 72.55 27.45 100.00 no 37 14 51 Arrhythmia survived died Total Mortality


logistic Mortality i.Arrhythmia

_cons .3783785 .1187262 -3.10 0.002 .2045689 .6998635 yes 4.571427 1.717224 4.05 0.000 2.189294 9.545522 Arrhythmia Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Mortalitu with arrhytmia is 63.4%, without arrhytmia 27.5%, OR 4.6, p<0,001, logistic regression

Cardiac failuretab Cardiac_failure

Total 152 100.00 yes 35 23.03 100.00 no 117 76.97 76.97 failure Freq. Percent Cum. Cardiac

23% had cardiac failure.

Relation to mortality:tab Cardiac_failure Mortality, row

48.68 51.32 100.00 Total 74 78 152 45.71 54.29 100.00 yes 16 19 35 49.57 50.43 100.00 no 58 59 117 failure survived died Total Cardiac Mortality


logistic Mortality i.Cardiac_failure

_cons 1.017241 .1880949 0.09 0.926 .7079964 1.461561 yes 1.167373 .4510988 0.40 0.689 .5473769 2.489618Cardiac_failure Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


There is no difference in mortality in patients with and without heart failure (50.4 vs 54.3 %, p=0.69).Metabolic acidosistab MAC

Total 152 100.00 yes 117 76.97 100.00 no 35 23.03 23.03 acidosis Freq. Percent Cum. Metabolic

77% had metabolic acidosis

Relation to mortality:tab MAC Mortality, row

48.68 51.32 100.00 Total 74 78 152 43.59 56.41 100.00 yes 51 66 117 65.71 34.29 100.00 no 23 12 35 acidosis survived died Total Metabolic Mortality


logistic Mortality i.MAC

_cons .5217391 .1857945 -1.83 0.068 .2596183 1.048507 yes 2.480392 .9970157 2.26 0.024 1.128164 5.453413 MAC Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Mortality with MAC is 56.4% and without MAC is 34.3%, p=0,029, logistic regressionLipaemia or TAGtab Lipaemia

Total 152 100.00 yes 37 24.34 100.00 no 115 75.66 75.66 TAG Freq. Percent Cum.Lipaemia or

24,3% had lipaemia

Relation to mortality:tab Lipaemia Mortality, row

48.68 51.32 100.00 Total 74 78 152 37.84 62.16 100.00 yes 14 23 37 52.17 47.83 100.00 no 60 55 115 or TAG survived died Total Lipaemia Mortality


logistic Mortality i.Lipaemia

_cons .9166667 .171121 -0.47 0.641 .6357865 1.321635 yes 1.792208 .6935527 1.51 0.132 .8394376 3.826382 Lipaemia Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Mortality with lipaemia is 62.2% and without it 47.8%, p=0,132Hyperkalemiatab Hyperkalemia

Total 152 100.00 yes 37 24.34 100.00 no 115 75.66 75.66 a Freq. Percent Cum.Hyperkalemi

24,3% had hyperkalemia

Relation to mortality:tab Hyperkalemia Mortality, row

48.68 51.32 100.00 Total 74 78 152 29.73 70.27 100.00 yes 11 26 37 54.78 45.22 100.00 no 63 52 115 ia survived died TotalHyperkalem Mortality


logistic Mortality i.Hyperkalemia logistic Mortality i.Hyperkalemialogistic Mortality i.Hyperkalemia

_cons .8253968 .1546464 -1.02 0.306 .5717177 1.191637 yes 2.863636 1.16136 2.59 0.009 1.29333 6.340543Hyperkalemia Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Mortality with hyperkalemia is 70.3% and without í 45.2%, OR 2.9, p= 0,009, logistic regressionLiver teststab Liver_tests

Total 152 100.00 yes 20 13.16 100.00 no 132 86.84 86.84 Liver tests Freq. Percent Cum.

13.2% of patients had elevated liver function tests

Relation to mortality:tab Liver_tests Mortality, row

48.68 51.32 100.00 Total 74 78 152 50.00 50.00 100.00 yes 10 10 20 48.48 51.52 100.00 no 64 68 132 tests survived died Total Liver Mortality


logistic Mortality i.Liver_tests

_cons 1.0625 .1850425 0.35 0.728 .7552412 1.494762 yes .9411765 .4516969 -0.13 0.899 .3674139 2.410941 Liver_tests Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


There is no difference in mortality of patients with (50%) and without (52%) elevated LFTs, p=0.9. Rhabdo (myo, ^CK)tab Rhabdo

Total 152 100.00 yes 85 55.92 100.00 no 67 44.08 44.08 (myo, ^CK) Freq. Percent Cum. Rhabdo

There are 56% pacients with signs of rhabdomyolysis.

Relation to mortality:tab Rhabdo Mortality, row

48.68 51.32 100.00 Total 74 78 152 44.71 55.29 100.00 yes 38 47 85 53.73 46.27 100.00 no 36 31 67 (myo, ^CK) survived died Total Rhabdo Mortality


logistic Mortality i.Rhabdo

_cons .8611111 .2109913 -0.61 0.542 .5327163 1.391946 yes 1.436333 .471214 1.10 0.270 .7550984 2.732163 Rhabdo Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Mortality of pacients with ( 55%) and without (46%) rhabdomyolysisis not different, p=0,27AKI (anuria, oliguria, ^creatinine)tab AKI

Total 152 100.00 yes 60 39.47 100.00 no 92 60.53 60.53 ) Freq. Percent Cum.^creatinine oliguria, (anuria, AKI

There are 39.5% of patients with AKI

Relation to mortality:tab AKI Mortality, row

48.68 51.32 100.00 Total 74 78 152 48.33 51.67 100.00 yes 29 31 60 48.91 51.09 100.00 no 45 47 92 e) survived died Total^creatinin Mortality oliguria, (anuria, AKI

logistic Mortality i.AKI

_cons 1.044444 .2178332 0.21 0.835 .6939938 1.571864 yes 1.023478 .3398187 0.07 0.944 .5338993 1.961992 AKI Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


There is no difference in mortality of patients with (51.7%) and without (51.1%) AKI, p=0.94Discoloration of urinetab Discoloration_of_urine

Total 152 100.00 yes 16 10.53 100.00 no 136 89.47 89.47 on of urine Freq. Percent Cum.Discolorati

10.5% had discoloration of urine.

Relation to mortality:tab Discoloration_of_urine Mortality, row

48.68 51.32 100.00 Total 74 78 152 31.25 68.75 100.00 yes 5 11 16 50.74 49.26 100.00 no 69 67 136 urine survived died Total ion of MortalityDiscolorat


logistic Mortality i.Discoloration_of_urine

_cons .9710145 .1665456 -0.17 0.864 .6937932 1.359006 yes 2.265672 1.282313 1.45 0.148 .7472029 6.869979Discoloration_of_urine Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Pacients with discoloration of urine had mortality of 68.8% as compared to 49.3% in the others, p=0.148.

Hepatomegaly or fatty infiltration of livertab Hepatomegaly

Total 152 100.00 yes 16 10.53 100.00 no 136 89.47 89.47 n of liver Freq. Percent Cum.infiltratio y or fatty Hepatomegal

There were 10.5% of patients withhepatomegaly or fatty infiltration of the liver.

Relation to mortalitytab Hepatomegaly Mortality, row

48.68 51.32 100.00 Total 74 78 152 18.75 81.25 100.00 yes 3 13 16 52.21 47.79 100.00 no 71 65 136 liver survived died Total on of Mortalityinfiltrati fatty ly or Hepatomega

logistic Mortality i.Hepatomegaly

_cons .915493 .1571588 -0.51 0.607 .6539324 1.281673 yes 4.733331 3.138757 2.34 0.019 1.290387 17.36256Hepatomegaly Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Patients with hepatomegaly or fatty infiltration of the liver had mortality of 81% and without it 48%, p= 0,019, logistic regressionPulmonary oedematab Pulmonary_oedema

Total 152 100.00 yes 4 2.63 100.00 no 148 97.37 97.37 oedema Freq. Percent Cum. Pulmonary

There were only 4 (2,6%) patients with pulmonary oedema.

Relation to mortality:tab Pulmonary_oedema Mortality, row

48.68 51.32 100.00 Total 74 78 152 0.00 100.00 100.00 yes 0 4 4 50.00 50.00 100.00 no 74 74 148 oedema survived died Total Pulmonary Mortality


All 4 patients with pulmonary oedema died, as compared to 50% of patients without pulmonary oedema. Fevertab Fever

Total 152 100.00 yes 29 19.08 100.00 no 123 80.92 80.92 Fever Freq. Percent Cum.

19% of patients had fever.

Relation to mortality:tab Fever Mortality, row

48.68 51.32 100.00 Total 74 78 152 13.79 86.21 100.00 yes 4 25 29 56.91 43.09 100.00 no 70 53 123 Fever survived died Total Mortality


logistic Mortality i.Fever

_cons .7571429 .1378616 -1.53 0.127 .529895 1.081847 yes 8.254717 4.692526 3.71 0.000 2.709087 25.15251 Fever Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Mortality of patients with fever is 86.2% as compared to 43% in patients without fever, p<0,001, logistic regression

Hypotensiontab Hypotension

Total 152 100.00 yes 45 29.61 100.00 no 107 70.39 70.39 Hypotension Freq. Percent Cum.

29.6% had hypotension

Relation to mortality:tab Hypotension Mortality, row

48.68 51.32 100.00 Total 74 78 152 35.56 64.44 100.00 yes 16 29 45 54.21 45.79 100.00 no 58 49 107 n survived died TotalHypotensio Mortality


logistic Mortality i.Hypotension

_cons .8448276 .163926 -0.87 0.385 .5775709 1.235751 yes 2.145408 .7871991 2.08 0.037 1.045165 4.403877 Hypotension Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Hypotensive patients had 64% mortality as compared to 46% in those without hypotension, OR 2.1, p=0.037, logistic regressionECG changestab ECG

Total 152 100.00 yes 102 67.11 100.00 no 50 32.89 32.89 ECG changes Freq. Percent Cum.

67.1% had Other ECG changes.

Relation to mortality:tab ECG Mortality, row

48.68 51.32 100.00 Total 74 78 152 39.22 60.78 100.00 yes 40 62 102 68.00 32.00 100.00 no 34 16 50 changes survived died Total ECG Mortality


logistic Mortality i.ECG

_cons .4705882 .142668 -2.49 0.013 .2597662 .8525099 yes 3.29375 1.201387 3.27 0.001 1.61145 6.732314 ECG Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


Mortality of patients with Other ECG changes was 61% as compared to 32% without them: OR 3.3, p<0.001

Multivariant analysisMissing values analysismisstable summarize Mortality Age Sex Child Male Resp_infection TBI Status_epilepticus Nontrauma_neuro_dg Other Average_dose Duration Cum_dose Arrhythmia Cardiac_failure MAC Lipaemia Hyperkalemia Liver_tests Rhabdo AKI Discoloration_of_urine Hepatomegaly Pulmonary_oedema Fever Hypotension ECG Catecholaminesmisstable summarize Mortality Age Sex Child Male Resp_infection TBI Status_epilepticus Nontrauma_neuro_dg Other Average_dose Duration Cum_dose Arrhythmia Cardiac_failure MAC Lipaemia Hyperkalemia Liver_tests Rhabdo AKI Discoloration_of_urine Hepatomegaly Pulmonary_oedema Fever Hypotension ECG Catecholamines

Cum_dose 24 128 85 3.24 1918.08 Duration 2 150 53 .66 264 Average_dose 24 128 44 1.5 15.2 Male 19 133 2 0 1 Child 1 151 2 0 1 Age 4 148 63 .02 71 Variable Obs=. Obs>. Obs<. values Min Max Unique

Most missing values (24) is for average dose.misstable patterns Mortality Age Sex Male Resp_infection TBI Status_epilepticus Nontrauma_neuro_dg Other Average_dose Duration Arrhythmia Cardiac_failure MAC Lipaemia Hyperkalemia Liver_tests Rhabdo AKI Discoloration_of_urine Hepatomegaly Pulmonary_oedema Fever Hypotension ECG Catecholaminesmisstable patterns Mortality Age Sex Resp_infection TBI Status_epilepticus Nontrauma_neuro_dg Other Average_dose Duration Arrhythmia Cardiac_failure MAC Lipaemia Hyperkalemia Liver_tests Rhabdo AKI Discoloration_of_urine Hepatomegaly Pulmonary_oedema Fever Hypotension ECG Catecholamines, frequency

Variables are (1) Duration (2) Age (3) Average_dose

100% <1 1 0 0 1 0 1 0 2 1 0 1 14 1 1 0 82% 1 1 1 Percent 1 2 3 Pattern

(1 means complete) Missing-value patterns

Variables are (1) Duration (2) Age (3) Average_dose

152 1 1 0 0 2 0 1 0 3 1 0 1 21 1 1 0 125 1 1 1 Frequency 1 2 3 Pattern

(1 means complete) Missing-value patterns

There are 125 (82%) patients with complete data set, but sex can be ignored, giving 128 cases with complete analysable data

Correlation analysis among variablesSymptomspwcorr Arrhythmia Cardiac_failure MAC Lipaemia Hyperkalemia Liver_tests Rhabdo AKI Discoloration_of_urine Hepatomegaly Pulmonary_oedema Fever Hypotension ECG Catecholamines, sig print(10)

0.0000 0.0020 0.0009 0.0001 ECG 0.8667 -0.2490 0.2666 0.3091 0.0073 0.0002 0.0001 Hypotension 0.2167 0.3018 0.3145 0.0006 0.0173 0.0523 0.0471 Fever 0.2741 0.1928 0.1577 0.1613 0.0166 Pulmonary_~a 0.1941 0.0600 0.0015 0.0236 Hepatomegaly 0.1529 0.2550 0.1836 0.0600 0.0022 0.0001Discolorat~e 0.1529 0.2470 0.3045 0.0055 0.0000 0.0070 0.0120 0.0004 AKI -0.2243 0.3895 0.2179 0.2033 0.2832 0.0091 0.0162 0.0001 Rhabdo 0.2110 0.1948 0.3064 1.0000 0.0039 Liver_tests 0.2327 1.0000 0.0100 0.0796Hyperkalemia 0.2083 0.1427 1.0000 0.0427 Lipaemia 0.1646 1.0000 0.0639 MAC 0.1507 1.0000 0.0007Cardiac_fa~e -0.2733 1.0000 Arrhythmia 1.0000 Arrhyt~a Cardia~e MAC Lipaemia Hyperk~a Liver_~s Rhabdo

0.0671 0.0008 0.0099 ECG 0.1489 0.2687 0.2087 1.0000 0.0002 0.0007 Hypotension 0.2941 0.2719 1.0000 0.0550 0.0008 0.0008 0.0037 Fever 0.1559 0.2699 0.2699 0.2340 1.0000 0.0000Pulmonary_~a 0.3454 1.0000 Hepatomegaly 1.0000 0.0000Discolorat~e 0.3370 1.0000 AKI 1.0000 AKI Discol~e Hepato~y Pulmon~a Fever Hypote~n ECG

Table shows correlation coefficients and p values. Only values with p<0.1 are displayed.

And now only parametrs influencing mortality in univariate analysis. pwcorr AgeOver55 Resp_infection TBI Other Average_dose_above5 Duration_3 Cum_dose_above360 Arrhythmia MAC Hyperkalemia Hepatomegaly Fever Hypotension ECG , sig print(10)

0.0000 0.0016 0.0006 0.0115 0.0000 0.0007 ECG -0.3946 0.2532 -0.2753 0.2229 0.3391 0.2949 Hypotension 0.0028 0.0006 0.0545 0.0082 0.0297 0.0811 Fever -0.2437 0.2761 -0.1563 0.2327 0.1776 0.1547 0.0000 0.0077 0.0066 0.0575Hepatomegaly 0.5901 -0.2154 0.2209 0.1683 0.0026 0.0192 0.0014 0.0504Hyperkalemia -0.2457 -0.1898 0.2564 0.1733 0.0124 0.0365 0.0979 MAC 0.2204 -0.1709 0.1469 0.0000 0.0141 0.0010 0.0003 0.0007 0.0195 Arrhythmia -0.3853 0.1988 -0.2652 0.3134 0.2727 0.2063 0.0000 0.0100 0.0650 0.0000 0.0000Cum_dose~360 -0.3906 0.2269 -0.1636 0.3846 0.4652 1.0000 0.0020 0.0445 0.0282 0.0000 Duration_3 -0.2536 0.1643 0.1793 -0.3996 1.0000 0.0001 0.0108 Average_do~5 -0.3354 0.2245 1.0000 0.0371 0.0013 0.0000 Other 0.1715 -0.2584 -0.3945 1.0000 0.0001 0.0013 TBI -0.3107 -0.2584 1.0000 0.0175Resp_infec~n -0.1951 1.0000 AgeOver55 1.0000 AgeOv~55 Resp_i~n TBI Other Averag~5 Durati~3 Cum_~360

0.0000 0.0009 0.0008 0.0099 ECG 0.8667 0.2666 0.2687 0.2087 1.0000 0.0073 0.0007 Hypotension 0.2167 0.2719 1.0000 0.0006 0.0008 Fever 0.2741 0.2699 1.0000 0.0600 Hepatomegaly 0.1529 1.0000 0.0100 Hyperkalemia 0.2083 1.0000 MAC 1.0000 Arrhythmia 1.0000 Arrhyt~a MAC Hyperk~a Hepato~y Fever Hypote~n ECG

Of note are following correlations: ECG changes and Arrhythmia (R=0.87, p<0,001). Indeed Cumulative dose was calculated from Average dose (R=0,38, p<0,001) and Duration (R=0,47, p<0,001)Hepatomegaly and Resp. infection, R= 0.59, p<0,001Other and TBI, R=-0,4, p<0,001TBI and Age over 55, R=-0,31, p<0,001Average dose and Age over 55, R=-0,34, p<0,001Cumulative dose and Age over 55, R=0,39, p<0,001Arrhytmia and Age over 55, R=-0,39, p<0,001Arrhytmia a ndAverage dose, R=0,31, p<0,001ECG and Age over 55, R=-0,39, p<0,001

For further analysis – Average dose and Duration is used and Cumulative dose is withdrawn. Arrhytmia and other ECG changes represent each other – only other ECH changes are used in the analysis.

Final model for logistic regressionlogistic Mortality i.Average_dose_above5 i.Duration_3 i.TBI i.MAC i.Fever

_cons .0147524 .0173524 -3.58 0.000 .0014711 .1479387 yes 4.763136 3.003413 2.48 0.013 1.384091 16.3916 Fever yes 2.624639 1.433293 1.77 0.077 .8999857 7.654265 MAC yes 4.169817 2.118244 2.81 0.005 1.540676 11.28555 TBI 3 10.8195 11.82321 2.18 0.029 1.270694 92.12413 2 17.00996 20.16467 2.39 0.017 1.665851 173.6883 Duration_3 1.Average_dose_above5 2.897614 1.418114 2.17 0.030 1.11034 7.561794 Mortality Odds Ratio Std. Err. z P>|z| [95% Conf. Interval]


coefplot, drop(_cons) xline(1) eformcoefplot, drop(_cons) xline(1) eform ciopts(recast(rcap))

Average dose above 5 mg/kg/hr

Duration 20-60 min vs <20 min

Duration >60 min vs <20 min

TBI

Metabolic acidosis

Fever

2001 2 3 4 5 10 50 10020Odds ratios (95% CI), log scale

estat classlroc

Correctly classified 75.78% False - rate for classified - Pr( D| -) 20.41%False + rate for classified + Pr(~D| +) 26.58%False - rate for true D Pr( -| D) 14.71%False + rate for true ~D Pr( +|~D) 35.00% Negative predictive value Pr(~D| -) 79.59%Positive predictive value Pr( D| +) 73.42%Specificity Pr( -|~D) 65.00%Sensitivity Pr( +| D) 85.29% True D defined as Mortality != 0Classified + if predicted Pr(D) >= .5

Total 68 60 128 - 10 39 49 + 58 21 79 Classified D ~D Total True

Logistic model for Mortality

0.

000.

250.

500.

751.

00S

ensi

tivity

0.00 0.25 0.50 0.75 1.001 - Specificity

Area under ROC curve = 0.8463

area under ROC curve = 0.8463number of observations = 128

Logistic model for Mortality

lsensestat ic

Note: N=Obs used in calculating BIC; see [R] BIC note . 128 -88.47268 -60.76946 7 135.5389 155.5031 Model Obs ll(null) ll(model) df AIC BIC

Akaike's information criterion and Bayesian information criterion

Additional calculationsFever and Average infusion ratetabstat Average_dose, by( Fever ) stat( N mean sd q min max)

Total 128 6.245938 2.833732 4 5.8 7.78 1.5 15.2 yes 27 7.603704 2.693365 5.5 7.5 10 3 15.2 no 101 5.88297 2.771504 4 5.5 7 1.5 15 Fever N mean sd p25 p50 p75 min max

by categories of: Fever (Fever)Summary for variables: Average_dose

graph box Average_dose , over(Fever) title("Fever")

05

1015

Ave

rage

dos

e (m

g/kg

.h)

no yes

Fever

regress Average_dose i.Fever, vce(robust)

_cons 5.88297 .2765756 21.27 0.000 5.335635 6.430305 yes 1.720733 .5825157 2.95 0.004 .5679519 2.873515 Fever Average_dose Coef. Std. Err. t P>|t| [95% Conf. Interval] Robust

Root MSE = 2.7556 R-squared = 0.0619 Prob > F = 0.0037 F(1, 126) = 8.73Linear regression Number of obs = 128

Patients with fever recieved higher propofol infusion rate (by 1.72 mg/kg/h; p=0.004).

part s1: table of published case reports of pris between ...10.1186... · web viewck 863.000iu/l,...

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