Paul E. Marik, MD, FCP(SA), FRCPC, FCCM, FCCP

Version 2.00Copyright, P Marik 2001©

Table of Contents

Intro/PrefaceDaily ManagementHyperglycemiaBlood Comp RxDVT ProphylaxisNutritionVentilator PneumoniaWeaningARDSSedationNeuromuscular Blockers

EBM ICU Protocols

By Paul Marik, MD TOC

Note to reader:The author has checked with sources believed to be reliable and up to date in an effort to provide information that is complete and generally in accord with standards of practice at the time of publication. However, in view of the possibility of human error or changes in medical science the author of this book cannot warrant that the information contained herein is in every respect accurate or complete. Readers are encouraged to confirm the information contained herein with other sources.

Disclaimer: Use at your own risk! Verify all information before initiating treatment. Feedback:Please e-mail comments, corrections or suggestions to pmarik@zbzoom.net

Evidence Based Critical Care Medicine:Balancing the Evidence

Before medicine developed its scientific basis of pathophysiology, clinical practice was learned empirically from the events of daily experience in diagnosing and treating the maladies patients presented. Students learned as apprentices to clinicians, observing the phenomena of disease, the skill of diagnosis and treatment, and the outcomes of different remedies. Sir William Osler's classic textbook of medicine was based almost entirely on his personal experience correlated with the general experience of others. With advances in our understanding of human physiology and the pathophysiologic basis of disease these remedies fell by the wayside and treatment became based on modalities of treatment that were shown to interrupt or otherwise modify the disease process. Until recently it was considered sufficient to understand the disease process in order to prescribe a drug or other form of treatment. However, when these treatment modalities were subjected to randomized controlled clinical trials (RCT's) examining clinical outcomes and not physiological processes, the outcome was not always favorable. The RCT has become the reference in medicine by which to judge the effect of an intervention on patient outcome, because it provides the greatest justification for conclusion of casualty, is subject to the least bias and provide the most valid data on which to base all measures of the benefits and risk of particular therapies. Numerous ineffective and harmful therapies have been abandoned as consequence of RCT's, while others have become integral to the care of patients and become regarded as the standard of care.

Many RCT's are, however, inconclusive or provide conflicting results. In this situation systematic reviews that are based on meta-analysis of RCT's are clearly the best strategy for appraising the available evidence. While meta-analysis have many limitations, they provide the best means of determining the significance of the treatment effect from inconclusive or conflicting RCT's. Although over 250,000 RCT's have been performed, for many clinical problems there are no RCT's to which we can refer to

answer our questions. In these circumstances we need to base our clinical decisions on the best-evidence available from experimental studies, cohort studies, case series and systematic reviews.

Intuition, anecdotes, common sense, personal experience and personal biases can no longer be used to justify clinical decisions or therapeutic policies. Every decision that the clinician makes must be based on sound scientific evidence (a collection of anecdotes is not scientific evidence). Many clinicians justify their c urrent practices by rationalizing that's the way I've been doing it for the last 20 years. However, nothing in medicine stands still, and its likely that the physician has been repeating the same mistakes for the last 20 years.

Top

The Need for Evidence Based Protocols in the ICU

The practice of medicine is characterized by enormous variability, frequently with opposing therapeutic strategies. Ambiguities in care may have disastrous implications for ICU patients who are managed by a large team of health care professionals. In order to achieve the best outcomes for these very complicated patients, it is essential that all members of the team have a common approach based on the best available current evidence.

The role of the ICU is to provide temporary physiologic support for patients who have suffered acute and often catastrophic insults. The care of these patients requires the coordinated and integrated support of all the organ systems and the prevention of the unique complications faced by these patients. As many of the management issues are common to most ICU patients a standardized evidence based approach to these issues will ensure a systematic and coordinated management strategy. Evidence based protocols prevent ambiguities in patient care, while allowing the individualization of the management of these exceedingly complex patients.

Contradictory therapeutic approaches have a negative impact on all the members of the team and compromise patient outcome. Changing the patients' therapy each time different members of the team see the patient results in fragmented care and undermines the team approach essential to achieving the best patient outcome. Protocols help avoid these ambiguities of care.

In order for this approach to succeed the protocols must be evidence based and have the full support of all members of the team. If disagreements exist these need to be resolved (by reviewing the literature) prior to the implementation of a protocol. Furthermore, protocols must evolve as clinical circumstances dictate and as new evidence emerges.

Top

Daily ICU Management

TOCDaily ExamNeuro ExamLabs & CXRPresentingKey Points

Intensive Care Units exemplify the miraculous advances of modern medicine. An ICU provides an environment where high-quality, compassionate, physiologically orientated and evidence based medicine can be practiced. The ICU is an exciting and challenging place to work and provides a remarkable learning environment. The keys to a successful rotation in the ICU are i) teamwork and ii) a systematic, disciplined and organized approach to patient care.

Admission History and Physical Examination

It is essential that a detailed and systematic history and physical examination (H+P) be performed on all patients admitted to the ICU. It is essential that the patients code status and the presence of advance directives be established on admission to the ICU.

The Daily Examination

It is essential that a thorough physical examination be performed daily, the following features should be documented:

General

Overall condition of patient The presence of all invasive lines, tubes and devices Vital signs:- temperature, including max. 24 hour temp, BP, pulse (rate+rhythm), RR. The presence of all pulses and the adequacy of peripheral perfusion Limb symmetry and swelling (presence of venous thrombosis) Presence of rashes and decubitus ulcers

Heart Heart sounds and murmurs.

Chest Symmetry of air entry and presence of rhonchi or crackles

Abdomen

The presence of distension and tenderness (esp. RUQ).

The type of enteral feeds should be recorded,evidence of reflux and the gastric residual volumes. Presence of diarrhoea should be noted.

CNS - A focused neurological examination is essential, particularly in patients receiving hypnotic/sedative agents, and should include the following:

Level of consciousness and response to commands Pupillary size and response Eye movements Limb movements; spontaneous and in response to noxious stimuli (pain) Presence of deep tendon reflexes

The Ventilator: The ventilator is an extension of the patient and it is therefore essential that the following features be recorded:

Mode of ventilation (AC, SIMV, PCV etc) Set rate & patient rate Tidal volume FiO2 PEEP Peak airway pressure and plateau airway pressure

Top

The importance of the daily neurological examination

Critically ill patients in the ICU are at risk of developing serious neurological complication including, ICU psychosis, septic encephalopathy, critical illness polyneuropathy, entrapment neuropathies, compartment syndromes, cerebral edema, intracerebral hemorrhages (related to coagulopathies), cerebral ischemia (related to hemodynamic instability) and cerebral embolism. These conditions can only be detected and diagnosed by physical examination. Furthermore, these conditions may frequently be masked in patients who are being sedated. It is therefore essential that the motor and eye response to a noxious stimulus (pain) as well as the deep tendon reflexes be recorded in all sedated patients. If the patient does not respond to a noxious stimuli the sedation must immediately be stopped, in order to facilitate further neurological evaluation.

The Glasgow Coma Scale (GCS) was developed to assess the level of consciousness of trauma patients. The GCS is a measure of pathologic obtundation. This scale is difficult to apply to intubated and sedated ICU patients. A description of the patients' level of consciousness (or arousal) and response to a noxious stimuli is more useful than documentation of the GCS. This description should include the type and power of the motor response.

Top

Laboratory tests and chest-radiographs

All ICU patients require a daily CBC, and urea and electrolytes Oxygenation - by pulse oximetry & blood gasses when appropriate All other laboratory tests should be ordered on merit All intubated patients require a daily chest radiograph. In all other patients chest radiographs should be ordered when indicated.

Top

Presenting on Daily Rounds

The presentation must be logical, sytematic, clear and succinct. The following approach is suggested:

1. Begin your presentation with the patient's name, sex and age. 2. List the primary medical problems responsible for ICU admission then, the list

significant secondary medical problems and chronic health problems 3. Outline the events of the past 24 hours 4. 24 hour urine output and fluid balance 5. Current Physical findings

BP, HR, RR, Temp & T.max General Chest Heart Abdomen CNS Extremeties

6. Ventilator settings and most recent blood gas [pH/pCO2/PO2/HCO3/Sat] or oxygen saturation

7. Relevant Labs 8. Review of medications 9. Assessment and plan.

Top

KEY POINTS:

1. ICU patients are at a high risk for DVT and therefore all ICU patients require DVT prophylaxis (i.e SQ heparin, s/q LMWH, compression stockings alone or in combination).

2. All ICU patients should be evaluated for risk factors for stress ulceration and high risk patients should receive stress ulcer prophylaxis.

3. All intubated patients require a gastric tube. The orogastric route is preferred.

Gastric tubes provide access to the GI tract for feeding, allow measurement of the residual volumes and allow decompressions of the stomach to minimize the risk of aspiration. Small bore tubes have no advantages over standard NG tube unless feeding is being given into the small intestine.

4. Determine the adequacy of venous access. 5. Don't forget to feed the patient; absent bowel sounds do not preclude enteral

feeding. 6. Communicate with the patients' nurse and respiratory therapist. 7. If you don't understand something, ASK!

Top

Stress-induced hyperglycemia

TOCIntroductionSliding ScaleInfusion

IntroductionStress-induced hyperglycemia is common in ICU patients. Hyperglycemia is associated with an increase risk of infections complications; recent evidenece suggests that the maintenance of euglycemia can reduce infectious complications and reduce the mortality of ICU patients.

Long-acting insulin has no role in the management of hyperglycemia in acutely ill ICU patients. In patients with mild stress induced hyperglycemia a s/c insulin sliding scale maybe appropriate. However, in many patients s/c insulin prevents large fluctuations in glucose level but rarely controls blood glucose in the 125-200 mg/dl range. For this reason a continuous insulin infusion is suggested. The target blood glucose is 125 to 200 mg/dl

6 Hourly Sliding Scale

BG ......... U s/c insulin < 150 ............. 0 150-200 ........ 2 (or 4) 201-250 ........ 4 (or 6) > 250 ............. insulin infusion

Top

Insulin Infusion Protocol

1. Mix 200 units regular insulin in 200 cc NS (= 1 U/cc) 2. Flush tubing with 50 cc of insulin saline infusion 3. Begin IV insulin infusion at a rate of 2 U/hr 4. Check capillary blood 1 to 2 hourly until stable then 4 to 6 hourly 5. Adjust infusion rate as follows:

i. If BG 80-124 mg/dl or if BG falls by > 50 mg/dl/hr

Rate(U/hr) ... DECR. by U/hr<2 ............................. 0.52-10 .......................... 1

10-20 ........................ 2> 20 .......................... 4

ii. If BG 125 to 200 mg/dl,continue current drip rate

iii. If BG > 200 mg/dl

Rate (U/hr) ... INCR. by U/hr< 2........................... 0.52-10 ........................ 110-20 ...................... 2> 20 ........................ 4

iv. For hypoglycemia

BG < 80 mg/dl STOP infusion, give ½ amp D50

BG < 60 mg/dl STOP infusion, give 1 amp D50

Repeat finger stick in 15 minutes and repeat D50 until BG > 100 When BG > 100, resume insulin infusion at 50% of prior rate

Top

BLOOD COMPONENT THERAPY

TOCRBCPlateletFFPCryoprecipitateDosingDICEPONotes

Indications for red blood cell transfusion (See note 1) Hb < 9 in patients with evidence of cardiac decompensation, unstable CAD, or Hx of CAD and preop Acute GI tract bleed with Hct < 30 Hb < 7.5 in all other ICU patients

Indications for platelet transfusion (See note 2) Chronic thrombocytopenia (< 5000) and patient bleeding Acute or chronic thrombocytopenia (< 10,000) and patient on chemotherapy Acute or chronic thrombocytopenia (< 50,000) and patient bleeding Acute or chronic thrombocytopenia (< 100,000) and operative bleeding Acute or chronic thrombocytopenia (< 50 -100,000 depending on procedure) undergoing invasive or operative procedure CONTRAINDICATED IN TTP

Indications for fresh frozen plasma (See note 3) Replacement of clotting factors when PT and or PTT 1.5 X control or greater and patient bleeding or facing hemostatic challenge Treatment of thrombocytopenic purpura (TTP) Treatment of ATIII deficiency Rapid reversal of warfarin effect C1 esterase inhibitor deficiency

Indications for cryoprecipitate (See note 4) Fibrinogen < 100 mg/dl and patient bleeding Hemophilia A or von Willebrand's disease

Dosing Guidelines for Blood Components

Fresh frozen plasma: 2 - 4 units (400-1000 ml) over 1 hour Platelets:Use whatever dose is necessary to increase platelet count above 50 000; 6 units is usually sufficient; or 1 unit or random platelets per 10 kg over 30 minutes Cryoprecipitate:desired increase in g/L= (0.2 X number bags)/plasma volume in L;

or use 1 bag/5kg, IV push or 1000u/10 min Packed red blood cells; 1 unit increases hemoglobin by 1.0-1.5 g/dL; give over 2-3 hours

Top

Rx of DIC

DIC is characterized by bleeding and widespread microvascular thrombosis. While the bleeding manifestations usually receive the most attention, the microvascular thrombosis are pathologically more important and strongly implicated in the development of organ failure.Blood component therapy is a potentially hazardous in patients with DIC as it adds fuel (thrombin & fibrinogen) to the fire. The administration of FFP and platelets should be restricted to patients with active hemorrhage and severe decreases in PT and platelet count AND should be coadministered with activated Protein C. Fibrinogen concentrates should be avoided.

Erythropoeitin (EPO) & ICU anemia

Anemia is common in ICU pateints. The casues are multifactorial, including low erythropoietin, blunted response to EPO, and venesection. rhEPO has been demonstrated to decrease the transfusion requirements of ICU patients.

Indications Pts expected to be in ICU > 3 days Hct < 36

Regimen On 2nd ICU day or when Hct < 36 40 000u s/c weekly PO iron daily (150 mg of elemental iron) IV iron should be considered if ferritin < 100 ng/ml despite PO iron

Monioring Baseline: Retic's, Fe, TIBC,ferritin Twice weely: Retics's, ferritin

Top

Notes:

1. There is a lack of reliable data to define "the ideal" hemoglobin concentration in critically ill patients. However, blood transfusion is associated with signifincat compliations, the most important being immunosupression. recent data suggests that the number of units of transfused blood may be an independent predictor of MSOF and death. Currently a transfusion "trigger" of 7-8 g/dl is reccommended.

However, patients with unstbale coronary artery disease or "cardiac decompensation" maybe at risk of silent ischemia at this level, and a transfusion trigger of 9-10 g/dl may be more appropriate in this group of patients.(Back to text)

2. Platelets should generally be reserved for thrombocytopenic patients who are BLEEDING and thrombocytopenic patients undergoing invasive or operative procedures.(Back to text)

3. Fresh frozen plasma contains all the stable and labile plasma constituents. One unit of FFP contains approximately 400 mg of fibrinogen and 1 U clotting activity per milliliter.(Back to text)

4. Cryoprecipitate is prepared from a cold insoluble precipitate of plasma. It contains high levels of factor VIII (both procoagulant activity and von Willebrand factor) and fibrinogen. Insufficient amounts of the other clotting factors are present to be of therapeutic value.(Back to text)

Top

DVT Prophylaxis

TOCIntroductionRisk 1Risk 2Risk 3Risk 4N/S

IntroductionICU patients have many of the risk factors for DVT. ICU patients who do not receive DVT prophylaxis have a high incidence of thromboembolic disease. Consequently routine DVT prophylaxis is recommended in all ICU patients. Within the ICU population a number of risk factors significancantly increase the risk of DVT, including obesity, trauma, neurosurgery and hip and knee surgery. The prophylactic strategy therefore depends upon the patients risk profile. While the optimal prophylactic approach for certain groups has yet to be determined, the results of recent RCT's form the basis for the current recommendations in specific risk groups. The recommendations in those risk groups which have not been subject to well conducted RCT's are based on the recommendations of "expert panels."Top

Risk Group 1 ICU patient NOT represented below

5000 U heparin s/c q 8 hourly .. Or External pneumatic compression

Risk Group 2 Obesity (BMI > 30) Deep sedation/paralysis GBS/M.gravis/Stroke Spinal cord injury Urological surgery Femoral catheters

External pneumatic compression and 5000 heparin s/c q 8 hourly .. Or Lovenox 40 mg s/c daily

Top

Risk Group 3 Total hip replacement Total knee replacement Fracture hip/femur

Trauma (excluding TBI) Lovenox 30mg s/c q 12 hourly .. Or Lovenox 30mg s/c q 12 hourly and external pneumatic compression (if feasible)

Risk Group 4 Intracerebral hemorrhage TBI Coagulopathy (PT or PTT > 1.5 x control) Active bleeding

External pneumatic compression

Neurosurgery Lovenox 40 mg s/c daily (started post-op) and external pneumatic compression/compression stockings

Top

Nutrition in the ICU

TOCPrinciplesProtocolNotesLiver failurePancreatitisRenal failure

"If The Bowel Works, Use It" .... "There is no disease process that benefits from starvation"

Principle of nutritional support in the ICU

1. Nutritional support is an essential component in the management of critically ill patients.

2. There is no data that TPN is of any benefit in critically ill patients. The available evidence suggests that TPN increases complications and mortality rates (see note 1). TPN should therefore be limited to patients, who after 5-7 days of starvation, are unable to tolerate even small volumes of enteral nutrition (EN). The addition of "trickle feeds" reduce the complications associated with TPN. Despite this data, patients with a functional gut continue to receive TPN!

3. Early EN (within 24 hours of admission to the ICU) has been shown to reduce complications and improve the outcome of critically ill patients when compared to delayed EN.No studies demonstrate an advantage to delaying nutritional support in seriously ill patients.

4. Over 20 RCT's have demonstrated that "immune enhancing diets" (IED) decrease indices of inflammation, improve cell mediated immunity, decrease organ failure and ICU complications, and reduce LOS. Immune enhancing diets should therefore be given to all patients with ALI/ARDS, sepsis, poly-trauma and other "high risk" patients with an anticipated ICU stay in excess of 5 days.

5. Overfeeding patients is associated with significant complications including hyperglycemia, hepatic steatosis with hepatic dysfunction, elevated BUN and excessive CO2 production.

6. There is no data to suggest that accurately measuring energy expenditure and nutritional requirements improves outcome.

Summary: "Do It early, Do It slowly and Do It with an IED"Top

Nutrition Protocol

EN should be initiated within 12 hours of admission to the ICU. Use IED in high risk patients Place NG tube. If a patient is at high risk for poor gastric emptying then a small bowel tube should be placed.

The head of the bed should be elevated to 30o to decrease the risk of aspiration. Feeding may be administered by boluses of 100-250 ml every two to four hours or by continuous infusion started at 25 to 30 ml/hr and increased by 10 to 25ml/hr every six hours as tolerated (i.e gastric residual volumes < 150 ml) until caloric goal is achieved (25 to 30 kcal/day). Gastric residuals should be measured every 6 hours with continuous feeding or prior to each bolus. If the gastric residual is > 150 ml and/or should the patient reflux, the stomach should be emptied, feedings held for 2 hours, and then restated at one-half the volume. Erythromycin (250 mg IV q 8 hourly) improves gastric emptying and should be started. Should the residual volumes remain high and/or the patient tolerate tube feeding poorly, post pyloric access should be obtained. In patients with discontinuity of the bowel TPN maybe indiated.TPN should be initiated slowly; 50% of goal first day, 75% second day, 100% 3-4th day. In addition TPN should not be suddenly stopped (may cause profound hypoglycemia). Standard TPN orders include:

Non protein calories:25-30 kcals/kg/day CHO: MAX 4mg/kg/day (± 1600 cals) Lipid: 4-12 kcals/kg/day Protein ~1.5 g/kg/day Vitamins and trace elements

Top

Notes:

1. TPN is associated with significant complications, including an increased incidence of infections, metabolic disturbances such as hyperglycemia, hypophosphatemia, hypokalemia and trace element deficiency; atrophy of the GIT mucosa and lymphoid system predisposing to bacterial translocation; immune suppression and hepatic dysfunction.(back to text)

2. Propofol emulsion contains 0.1g of fat (1.1 Kcal) for every milliliter. An infusion of propofol may therefore provide a significant caloric load. In patients receiving high dose propofol infusions, the enteral feeds need to be adjusted to take into account the added caloric load. A low-fat enteral formulation, such as Vivonex (10g fat/L) may be used.

3. The refeeding syndrome: Feeding malnourished patients, particularly after a period of starvation may result in severe metabolic disturbances, most notably hypophosphatemia. Hypophosphatemia developing after initiating parenteral or enteral nutrition has been termed the refeeding syndrome. In addition to hypophosphatemia, changes in potassium, magnesium and glucose metabolism occur during refeeding. Although classically described in cachectic patients after prolonged starvation, this syndrome has been reported to occur commonly in poorly nourished ICU patients who have been starved for as short as 48 hours.

Top

Nutrition in specific disease states

Liver FailureThe use of protein restriction in hepatic encephalopathy/liver failure is controversial. Intolerance of dietary protein should be balanced against the increasing evidence that adequate nutrition, including fair amounts of protein, can improve clinical outcome in patients with hepatic encephalopathy. Therefore, in patients with liver cirrhosis and hepatic encephalopathy, one should initially restrict daily protein intake to 0.5 g/kg/day and slowly increasing the intake to 1.0 g/kg per day. Zinc deficiency is common in patients with cirrhosis; supplement with 600mg zinc sulphate daily.

Pancreatitis Despite the lack of prospective data, "conventional wisdom" dictates that gut rest with or without the provision of parenteral nutrition remains the treatment of choice in acute pancreatis. However, the results of a number of RCT's has disproved this standard dogma. These studies have clearly demonstrated that oral feeds in mild/moderate pancreatitis and enteral feeding via a nasoenteric tube placed distal to the ligament of Treitz in patients with severe pancreatitis reduces indices of pancreatic and systemic inflammation and reduces the incidence of intra-abdominal sepsis, multiple organ failure, need for operative intervention, and mortality when compared with the parenterally fed patients. TPN consequently appears to have little (NO) role in the management of patients with acute pancreatitis. Oral refeeding is only recommended once pain has subsided and the serum amylase has approached normal levels.

Renal FailureMost patients with ARF are hypercatabolic and require increased quantities of nutrients. Patients with ARF should receive a minimum of 1g protein/kg/day and optimal non-protein calories. Protein intake in critically patients should not be limited in an attempt to avoid initiation of dialysis.

Top

Approach to Suspected VAP

TOCIntroductionPSB samplingBacteriologyEmpiric RxPSB Results

Introduction: Clinical criteria alone are notoriously unreliable in the diagnosis of VAP; consequently many patients without pneumonia are needlessly treated with antibiotics. Sputum culture (tracheal aspirate-T/A) should not be used to diagnose VAP as this test is plagued by both high false-positive and false-negative results; the specificity of sputum culture is only 50% (no better than flipping a coin).

Consequently, lower respiratory tract sampling together with quantitative culture is recommended to diagnose VAP. This can be performed bronchoscopically or blindly; the blind technique (B-PSB) has operating characteristics similar to the bronchoscopic technique; however, it is quicker, safer, more cost effective and easier to perform.

Patients with suspected PCP, immunocompromised and/or neutropenic patients should undergo formal bronchoscopy with PSB and BAL. T/A are suitable specimens in patients with suspected tuberculosis. Post-intubation T/A's may be useful for the diagnosis of community acquired pneumonia.Top

Indications for PSB sampling:

1. Patient intubated for greater than 24 hours 2. New or progressive pulmonary infiltrate on the chest radiograph (NO infiltrate, NO

VAP) 3. At least two of the following clinical criteria:

Fever > 38.3C (101F) Leukocytosis (> 10 x 109/L) Purulent tracheal secretions

Contraindications to Blind PSB:

1. Non intubated patients 2. Patients with uncontrolled bleeding 3. Ptients with PT/PTT greater than twice normal or a platelet count < 60 000 4. Ptients with known or suspected intrabronchial lesions 5. Patients who have recently undergone a pneumonectomy or lobectomy

Top

Blind PSB Procedure:

1. Administer 80 to 100% oxygen throughout the procedure and monitor O2 sats. 2. Midazolam/propofol should be administered to non-sedated patients to limit

coughing during the procedure. 3. A standard microbiology specimen brush is inserted through the ET tube until

approximately 35cm or until resistance is met. 4. A specimen is obtained by advancing the inner canula (expressing the wax plug),

advancing the brush, twisting the brush then retracting the brush into the inner canula.

5. The entire catheter is then removed from the ET tube. 6. The brush is then cut and placed in 1 ml of ringers lactate and processed by the

microbiology laboratory within 30 minutes. 7. Quantitative culture should be performed using standardized techniques.

Bacteriology of VAP

A consistent pattern of pathogens has been reported in patients with VAP. The commonest pathogens are:

S. aureus P. aeruginosa Enterobacter spp. S. pneumonia H. influenzae E. coli Klebsiella spp A. baumannii.

P. aeruginosa and A. baumannii are more common in patients intubated > 4 days while S. pneumonia and H. influenzae are more common in patients intubated for < 4 days. Anaerobes have been shown to be unimportant in most patients with VAP.Top

Empiric antibiotics until culture data available

The choice of empiric antibiotics is extremely important in determining the outcome of patients with VAP and should be based on local epidemiological data. The empiric regimen must be broad to cover the most likely pathogens; the appropriateness of the initial regimen determines outcome. This regimen is then tailed once culture data are available. A number of studies have demonstrated that the scheduled change (every 4-6 months) of antibiotic class can reduce both the incidence of VAP and the incidence of VAP attributed to antibiotic-resistant bacteria.

The following antibiotic(s) are reccommended. These reccommendations require modification depending on the importance of MRSA and pseudomonas in individual

ICU's. Rotating antibiotics is reccommended.

Piperacillin/Tazobactam ± vancomycin ± gentamycin Imipenem ± vancomycin ± gentamycin Ciprofloxacin ± vancomycin ± gentamycin

The use of 3rd generation cephalosporins should be limited due to the induction of ESBL and VRE.Top

Interpretation of PSB results

The results of the b-PSB should be recorded and interpreted as follows:

1. no growth 2. <500 cfu/ml (contaminant) 3. 500-1000 cfu/ml (borderline +ve) 4. > 1000 cfu/ml (positive)

Patients with borderline +ve or +ve culture should be considered to have VAP. Candida or coagulase negative staphylococci should be ignored. In patients with +ve and borderline +ve cultures the antibiotic regimen MUST be tailored/narrowed according to the sensitivities of the pathogen(s) isolated. In patients with negative cultures, the decision to continue or stop the antibiotics should be made by the patients' attending physicians based on his/her assessment of the risk of stopping antibiotics. However, it is recommended that unless VAP is strongly suspected, antibiotics be stopped and the patient re-cultured if a strong index of suspicion for VAP still exists.

Top

ARDS

TOCDefinitionsLow TVPCVHemo supportSedationOther RxChronicLung Protection

Definitions

ARDS/ALI is a condition characterized by:

An oxygenation defect with bilateral alveolar infiltrates A patient who has suffered an acute catastrophic event A patient with a PCWP < 18 mmHg and/or no clinical evidence of an elevated left atrial pressure

ALI:- PO2/FiO2 < 300ARDS:- PO2/FiO2 < 200

Rx of acute phase

The management of ARDS is essentially supportive and includes:

Cardio-respiratory and nutritional support The prevention of further lung injury The prevention of complications

Top

Ventilation

See Lung Protective Strategy

Initiating a Lung Protective Strategy

Patients with bilateral pulmonary infiltrates and any of the following ventilator parameters on standard assist-controlled ventilation should be be switched to PCV/low TV vent.:

Plateau pressure > 35 cmH2O PEEP > 10 cmH2O

FiO2 > 60%

Top

Low TV ventilation

Initial settings:

Adequate sedation must be achieved Mode: AC Tidal volume: 8ml/kg reduced by 1ml/kg to 4-6 ml/kg Rate: Set to match initial MV (max 30/min) FiO2: Original setting titrate Sats > 88% PEEP: Best determine by static PV curve, else by FiO2

FiO2 40 -- 8 FiO2 50 -- 10 FiO2 60 -- 12 FiO2 > 60 -- 15

Flow rate (I:E): Flow rate adjusted to achieve I:E of 1:1 - 1:1.3

Goals:

Plateau Press < 35 cmH2O Sat > 88% pH > 7.15

Top

Pressure Controlled Vent.

Required equip:

Ventilator that supports PCV Ventilator with wave-form capabilities Ventilator that can measure auto-PEEP Continuous pulse oximetry End-tidal CO2 monitoring

Initial PCV settings:

Adequate sedation must be achieved An inspiratory pressure of 20 cmH2O PEEP 15 cmH2O (if possible obtain a static pressure/volume curve and set PEEP above the lower inflection point) Same FiO2 as on A/C ventilation Rate 14/minute

Set inspiratory time such that the initial I:E is 1:1.5

Top

Refining the initial settings:

The inspiratory and expiratory times ( I:E ratio) and respiratory rate are best adjusted by analyzing the Flow vs. Time Waveform. It is essential that adequate inspiratory time be given so that all the airways, both healthy and diseased, have time to reach the preset pressure level. If expiration begins before flow has reached zero the inspiritary time needs to be increased. This will therefore increase mean alveolar pressure and improve oxygenation. The inspiratory time can be lengthened in 2 ways;

Increase the inspiratory time until the inspiratory flow reaches zero (recommended method) Reducing the "E" part of the I/E ratio will increase "I".

If flow reaches zero and there is a long inspiratory pause, this is an indication that inspiratory time is too long. Setting inspiratory time longer than that which is required to open recruitable airways increases the likelihood of significant auto-peep. To evaluate the adequacy of the expiratory time, the Flow vs. Time Waveform needs to be studied again. This waveform shows whether the patient has enough time to exhale to the pre-set PEEP level before the ventilator gives the next breath. Should inspiration begin before flow reaches zero air trapping will occur with the development of auto-PEEP. There is no data that intrinsic PEEP has any advantage over extrinsic (ie applied) PEEP. However, the unrecognized development of auto-PEEP may result in hemodynamic compromise leading to the inappropriate use of fluid and vasopressor therapy. Air trapping is corrected by either reducing the respiratory rate or inspiratory time. Each should both be independently and sequentially reduced, in order to determine which maneuver affects ventilation the least.

Top

Monitoring PCV

It is essential that the e TV be monitored and the ventilator alarms set at the appropriate level Continuous end-tidal CO2 monitoring is essential.These measures are important as changes in airway/lung compliance will result in a fall in tidal volume and increase in PaCO2 without this being clinically obvious. It is essential that the level of auto-PEEP be measured. Continuous pulse oximetry is essential with the arterial saturation kept above 88%. The Flow vs Time waveform should be monitored regularly. As the patients pulmonary mechanics change the inspiratory time and respiratory rate may need to be altered. Arterial blood gas analysis should be performed at least once daily.

Top

Hemodynamic support

The optimal fluid strategy in patients with ARDS is a hotly debated subject with a "wet lung" and a "dry lung" camp. These two approaches have as yet to been compared in an adequately powered RCT. In the absence of such data, "experts in the field" suggest a strategy that maintains the lowest intravascular volume (or PCWP) that sustains an adequate cardiac output (and renal perfusion). Inotropic agents may be required to maintain an adequate cardiac output and perfusion pressure (MAP > 75-80 mmHg). If hemodynamics allow the patient should be kept in a negative fluid balance. Once hemodynamic stability is achieved the patient should be actively diuresed (until the BUN climbs to approximately 30 mg/dl).

Sedation

All patients receiving low-volume/high PEEP ventilation require deep sedation to achieve ventilator synchrony. Sedation is best achieved with a continuous infusion of propofol and lorazepam supplemented with fentanyl as required.Neuromuscular blocking agents are associated with signifincat complications are their use is strongly discouraged.

Top

Other supportive measures:

GI prophylaxis DVT prophylaxis Early initiation of enteral nutrition with an immune enhancing formula Screen for nosocomial infection esp VAP

Top

Rx of Chronic Phase

Patients who after 10-14 days of aggressive supportive therapy require high levels of ventilatory support (FiO2 50%) are candidates for corticosteroid therapy. Corticosteroids should only be considered if lower respiratory tract sampling can be performed to diagnose and treat pulmonary sepsis. Prior to embarking on corticosteroid therapy sepsis should be excluded. Once corticosteroids are commenced surveillance cultures and protected lower respiratory tract sampling performed every 4th day.

Corticosteroid Protocol (methylprednisolone):

Days 1-14: Loading dose of 2mg/kg then 0.5 mg/kg q 6 hourly

Days 15 -21 1 mg/kg/day

Days 22-28 0.5 mg/kg/day

If patient extubated prior to day 14, treatment is tapered after day 15.

Top

Lung Protective Strategy

Because a significant portion of the lung is consolidated and not recruitable, only a small amount of aerated lung receives the total tidal volume - ARDS leads to "baby lungs". The use of traditional tidal volumes (12 to 15 ml/kg) in these patients will result in high inspiratory pressures with overdistension of the normally aerated lung units. An impressive body of experimental and clinical evidence has clearly demonstrated that mechanical ventilation that results in high trans-pulmonary pressure gradients and overdistension of lung units will cause acute lung injury. Animal studies have demonstrated that a trans-pulmonary pressure in excess of 35 cmH2O will lead to alveolar damage. Furthermore the cyclic opening and closing of lung units (recruitment and derecruitment) in patients with ARDS who are ventilated with insufficient PEEP will further potentiate this iatrogenic lung injury. It has clearly demonstrated that ventilatory strategies that avoid overdistension of lung units and also avoids end-expiratory alveolar collapse limits the degree of lung injury in ARDS, reduces complications and improves survival.

A relative form of "lung rest" using low tidal volume mechanical ventilation is therefore recommended. This may be achieved with low-volume, volume-cycled ventilation with a decelerating inspiratory flow or pressure controlled ventilation (PCV).

Permissive hypercapnia.The strategy to reduce volume induced lung injury by using small tidal volumes may lead to CO2 retention. The term "permissive hypercapnia" has been used to the describe this ventilatory strategy. Hypercapnic acidosis is generally well tolerated by the patients, especially when it develops gradually over 1 to 2 days. Aministration of bicarbonate to correct the acidosis is not reccommended. Permissive hypercapnia should not be used in patients with acute intracranial pathology.

Top

Protocol for Liberation/Weaning From Mechanical Ventilation

TOCStep 1Step 2Step 3Failure to weanNotes

Introduction

A number of different approaches to ventilator liberation have been reported (See note 1). The most popular and efficient method is described. According to this approach:

1. All ICU patients are screened daily by the RT (See note 2)2. Suitable patients undergo a 3 minute spontaneous breathing trial 3. This is followed by a 30 minute to 2 hour spontaneous breathing trial in those who

pass the 3 minute test

Step 1. Screening of patients

Candidates for the 3 minute spontaneous breathing trial: (See note 3) Adequate gas exchange

Non COPD: a PaO2 > 60mmHg with a FiO2 of 0.4 or less (PaO2/FiO2> 150) COPD: pH > 7.30, PaO2 > 50mmHg with a FiO2 of 0.35 or less

PEEP < 6 cmH2O Alert and cooperative patient.Patient not on a continuous infusion of sedatives/narcotics Temperature < 38C and > 36.5C No requirement for vasopressor agents

dopamine > 10 ug/kg/min norepinephrine

Minute ventilation < 15 L/min and RR < 30 Adequate cough during suctioning Heart rate less 100 beats/min Systolic blood pressure > 90 and < 180 mmHg

Top

Step 2. Three minute spontaneous breathing trial

Patients who meet all the above criteria then undergo a 3 minute spontaneous breathing trial.The patient will be placed on one of the following trial modes:

CPAP with auto-flow CPAP with pressure support of 5cm/H20 (See note 4)

The FiO2 is set at the same level as that used during mechanical ventilation. Trial must be monitored by pulse oximetry and electrocardiography. The trial must be stopped immediately when the patient meets any of the following criteria:

Resp Rate/Tidal Volume (Liters) > 105 Respiratory rate < 8 or > 35 Spontaneous tidal volume < 4cc/kg Arterial saturation < 90% Heart rate > 140 or heart rate change (either direction ) > 20%; no arrhythmia

Top

Step 3. Trial of Liberation

Patients continue to breath through the CPAP circuit. The FiO2 may be increased up to 50%.Back-up apnea parameters must be set on the ventilator to activate at a 20 second apneic interval.

Trial terminated when: Respiratory rate > 35/min Arterial saturation < 90 Heart rate > 140 or heart rate change (either direction ) > 20% or arrhythmias SBP > 180 and < 90 Increased anxiety and diaphoresis

Should the patient tolerate the CPAP trial for 2 hours (some studies have used 30 minutes) then the patient may be extubated.The trial is repeated daily in those patients who fail to tolerate this spontaneous breathing trial.The time to liberation is not shortened by repeating the spontaneous breathing trial multiple times per day.The ICU team must be notified should the patient pass this phase of the liberation process and an order obtained to extubate the patient.Orogastric tubes, if present should be removed to reduce the risk of aspiration. If gastric access is required a naso-gastric tube should be placed. The tube feeds should be stopped at this point in time. Intravenous glucose must be given to prevent hypoglycemia.

Top

Treatable causes of "failure to wean"

Hypophosphatemia Hypokalemia Hypomagnesemia Hypocalcemia (ionized) Pulmonary edema Angina Anemia Malnutrition Overfeeding with excessive carbohydrate (increased CO2 production)

Notes:

1. Weaning/liberation is the process by which a patient is removed from the ventilator. In many patients ventilatory assistance need not be decreased gradually, mechanical ventilation and artificial airways can simply be removed (liberated). According to this thesis patients can simply be removed from the ventilator once the disease process which led to intubation and mechanical ventilation has improved or resolved; a prolonged "weaning process"is therefore not required."Several studies have been performed comparing the efficacy of SIMV, T-piece/CPAP, and PSV weaning. No technique has proven superior to T-piece/CPAP weaning.Cinical judgement alone does not accurately predict whether mechanical ventilation can be discontinued successfully.It has recently been demonstrated that screening patients daily to identify those who can breathe spontaneously will promote earlier weaning from mechanical ventilation.(Return to text)

2. These are screening criteria; some patients who fail to meet these criteria may be candidates for the "three minute trial" if approved by the ICU medical team.(Return to text)

3. Patient evaluations should begin early in the morning (around 5:00 am) and the patients who meet the inclusion criteria will then immediately begin this protocol. Attending physicians will be notified during morning rounds with an update of all evaluated patients.(Return to text)

4. Patients with cardiac disease are best weaned with CPAP and pressure support; this includes patients with cardiac failure and patients with significant coronary artery disease. The level of pressure support should initially be set at between 10-12 cmH20 and reduced by 2 cmH20 until the patient is able to tolerate a PSV of 5 cm H20 for 2 or more hours. An electrocardiogram should be obtained prior to extubation in patients with a history of coronary artery disease.(Return to text)

Top

Sedation in the ICU

TOCIntroductionAssessmentSAS ScaleAgentsProtocol

Introduction

Anxiety is an almost universal feature of ICU patients. Consequently, sedation is an integral component of the management of the ICU patient. The primary objectives of sedation is too allay anxiety, enhance patient comfort, promote sleep, reduce O2 consumption, reduce the stress response, and facilitate mechanical ventilation. The desirable level of sedation/hypnosis will depend in large part upon the patient's acute disease process as well as the need for mechanical ventilation.

In anxious patients it is important to exclude treatable causes of anxiety and not just increase the amount of sedative drugs being used. Treatable causes of anxiety include:

Uncontrolled pain (NB) Ventilator settings inappropriate (esp inadequate flow rate) - respiratory incoordination Drug or alcohol withdrawal syndrome Increased work breathing, e.g. pneumothorax, kinked/blocked tube Pulmonary edema Loud ventilator alarms and monitors Poor communication with patient as regards diagnosis, therapy etc.

Top Assessing the degree of sedation and titrating the drug regimen to predetermined end-points is essential as both over sedation and inadequate sedation are associated with significant complications.

Complications of under-sedation include: Severe anxiety with delusional behavior nterference with medical and nursing care Sympathetic over-activity with increased myocardial oxygen consumption Self-injury Self-extubation

Complications of over-sedation include: Prolonged intubation with an increased risk of pulmonary complications Disorientation and "ICU-psychosis" following emergence Masking of significant neurological and neuromuscular complications

Top

Assessing the level of sedation

Ongoing clinical evaluation is the most effective method of assessing sedation. In order to provide a more consistent and objective means of assessing the degree of sedation a number of "sedation scales" have been used. The Glasgow Coma Scale (GCS) was developed to assess the level of consciousness of trauma patients. This scale is commonly used to monitor the level of sedation in ICU patients. The GCS is, however, essentially a measure of pathologic obtundation and cannot be recommended for monitoring sedation. The Sedation-Agitation Scale (SAS) was developed and tested on ICU patients and designed specifically for evaluating the level of sedation in the ICU. This is the preferred assessment scale.Top

The Sedation-Agitation Scale (SAS)

1. Unarousable - deep hypnosis, non-rousable, no spontaneous movement, no coughing

2. Very sedated - rousable with strong tactile stimulus, occasional spontaneous and non-purposeful movements, does not respond to commands

3. Sedated - Asleep/sedated but rousable with tactile stimulus and displays purposeful movements and follows simple commands

4. Calm cooperative - Calm, awakens easily, follows commands ------------------ 5. Agitated - Anxious or mildly agitated, attempting to sit up, calms down to verbal

instructions 6. Very agitated - Does not calm despite frequent verbal remind; requires physical

restraints, biting ET tube 7. Dangerous agitation - Severe anxiety, diaphoresis, frequent vigorous movements,

pulling on ET tube , trying to remove catheters, climbing over bed rails, striking at staff, thrashing side to side

Goals of Sedation

Non-ventilated patients SAS 3-4

Ventilated pts: AC, SIMV, PS SAS 2-4

Ventilated pts: PCV, low TV AC SAS 1-2

Top

Sedative/Hypnotic agents of choice

The following drugs have been selected based on cost, efficacy, tolerance, pharmacokinetics and pharmacodynamics and side-effects.

1. Long term sedation

Lorazepam is the drug of choice for non-intubated patients and patients who will require long term sedation/hypnosis in the ICU (> 48 hours). Benzodiazepines should be avoided in patients with liver disease. Lorazepam and propofol act synergistically; the addition of propofol should be considered to prevent oversedation and long waking time.

2. Short term sedation, neurological/neurosurgical patients

Propofol is the drug of choice due to the rapid emergence once discontinued

3. Deep hypnosis to facilitate "lung protective ventilation"

This may be achieved with propofol alone. However, propofol and lorazepam have synergistic effects and the combination may achieve the desired level of hypnosis at a lower cost.

4. Treatment of Delirium or sedation without respiratory depression

Haloperidol

5. Sedation for invasive procedures

Midazolam alone or in combination with fentanyl

The daily interruption of sedative-drug infusions is recommended in patients receiving mechanical ventilation. This approach allows daily assessment of neurological function that would otherwise not be possible and prevents oversedation and reduction of total sedative dosages.Top

Sedation Protocol

1. To treat SAS 7, sedation for PCV, neurosurgical/neurology patients , patients with hepatic dysfunction and short term sedation (< 24 hours)

Propofol: Start IV drip at 10ug/kg/min, titrate dose by increments of 5-10 mcg/kg/min at 10 minute intervals Lorazepam 2-4 mg IV Q4 hour; hold if patient requiring < 50 mcg/kg/min propofol Hold propofol drip Q AM to assess neuro status, restart drip at previous level Check triglyceride Monday and Thursday: if > 400 mg/dl halve propofol dose and start lorazepam infusion at XX mg/hr (if > 600 mg/dl stop propfol)

2. To treat SAS 5 or 6 or for any patient for whom sedation is required

Non Intubated patient Lorazepam 2-4 mg IV Q 6 hours. Hold for SAS < 3

Intubated Patient SAS 6. Lorazepam infusion - start at 2mg/hr and then titrate to SAS level XX increasing by 2mg/hr no more frequently than every 15 minutes. SAS < 6. Lorazepam 2-4 mg Q 4 hourly IV. If poor response change to an infusion of lorazepam at 2mg/hr and then titrate to SAS level XX increasing by 1mg/hr no more frequently than every 15 minutes. Hold lorazepam drip Q AM to assess neuro status, restart drip at previous level.

3. Delerium Haloperidol 5-25 mg IV Q 10 minutes PRN for SAS 6 or 7. DO not exceed 80 mg over 2 hours Haloperidol 5-25 mg IV Q 4 hours. Hold for SAS < 3

Note: Propofol should only be used in intubated patients

Weaning propofol

Decrease propofol by 10ug/kg/min q 2 hour IF SAS > 4 choose from:

Lorazepam 2-4 mg IV Q 4 hours. Hold for SAS < 3 Haloperidol 10 mg IV Q 10 minutes PRN for SAS 6 or 7. DO not exceed 80 mg over 2 hours Haloperidol 5 mg IV Q 4 hours. Hold for SAS < 3

Top

Neuro-muscular blockers in the ICU

TOCIntroductionNMBA'sTOF

Introduction

NMBA have historically been used in the OR where they have been found to be remarkably safe. The safety of these drugs in the ICU has been questioned, due to the increasing number of case reports of prolonged paralysis following their use. In particular, the concomitant use of NMBA and corticosteroids has been linked to a syndrome known as "acute quadriplegic myopathy". This syndrome may occur after use for as short as 8 hours and without the concomitant use of corticosteroids. Acute quadriplegic myopathy has been associated with the use of both steroid and non-steroid based NMBA. NMBA's should, therefore, be used only when absolutely indicated (and only when high dose propofol has failed) and then only for the shortest possible period of time. Neuromuscular blockade should NEVER be used for the treatment of anxiety or restlessness.

The major indication for NMBA in the ICU is to facilitate ventilation in the following circumstances:

High PEEP When peak airway pressures are high PCV Low tidal volume ventilation

To prevent excessive and prolonged neuromuscular blockade all patients receiving NMBA should be monitored using a nerve stimulator. For practical purposes the Train-Of-Four (TOF) should be used to access the degree of neuromuscular blockade. The goal is to achieve one to two twitches.

Top

Choice of NMBA

Long term paralysis

Vecuronium - duration 60-75 minutes Intubation: 0.07-0.1 mg/kg Maintenance: 4-10 mg/hr

Renal failure

Atracurium - duration 45-60 minutes Intubation: 0.4-0.5 mg/kg Maintenance: 20-50 mg/hr

Intubation

Rocuronium - acts 1 min, duration minutes 0.6-1.2 mg/kg

Succinylcholine - acts 30s, duration 5-15 minutes. 1mg/kg

CONTRAINDICATIONS to the use of Succinylcholine include:

Renal failure Burns Severe trauma with muscle injury Severe sepsis Ocular injuries severe acidosis

Top

Train of Four (TOF) Monitoring

The train of four (4 stimuli 0.5s apart) is a convenient way of monitoring the degree of neuromuscular blockade and roughly correlates with the degree of neuro-muscular junction receptor occupation:

4 twitches ... 0-70% receptors occupied 3 twitches ... 70-80% receptors occupied 2 twitches ... 80-90% receptors occupied 1 twitch ... > 95% receptors occupied 0 twitches ... 100% receptors occupied

In principle, any superficially located peripheral motor nerve can be stimulated. The ulnar nerve is however the most popular site. The electrodes are best applied on the volar side of the wrist.

From a practical point of view 1 to 2 twitches (of TOF) of the adductor pollicis muscle will result in sufficient diaphragmatic paralysis to prevent the patient from coughing, hiccoughing and breathing during mechanical ventilation.

Prior to paralysis the supramaximal stimulation (SMS) must be determined. The SMS is defined as the level at which additional stimulation current does not increase the twitch response. It is important to note that each nerve may have a different SMS and inadequate stimulation may lead the clinician to overestimate the degree of

neuromuscular blockade present. The SMS is usually in the range of 20-60 mA.

Starting at 10 mA, increase the TOF current by 10mA until four equal responses are obtained. Continue to increase the current until the intensity of the response does not increase any further. When this occurs the prior setting will be the SMS for that nerve. Once the patient is paralyzed the TOF is then performed using the SMS.

Top

The TOF test should be performed hourly until the goal is achieved (1-2 twitches) and then 6 hourly. The rate of the infusion should be adjusted as follows:

0 twitches Stop infusion, restart when 2 twitches are present. Restart infusion rate at:

80% if takes 1 hour for 2 twitches 75% if takes 2 hour for 2 twitches 50% if takes 3 hour for 2 twitches 25% if takes 4 hour for 2 twitches

1 twitch Reduce to 80% of present infusion rate

2 twitches Maintain present infusion rate

3 twitches Reload with 25% of loading dose Increase infusion rate by 25%

4 twitches Reload with 50% of loading dose Increase infusion rate by 50%

Top