1. 1. Medicine in Mind Maps Medical Science made incredibly simple
2. 2. abdominal trauma - assessment [created by Paul Young 28/10/07] initial assessment imaging and laboratory studies definitiontrauma series: - CXR identifies haemothorax, pneumothorax and pulmonary contusion - AP pelvis can confirm presence of significant pelvic fracture - lateral c-spine can identify non-survivable neck injury resuscitation & comprehensive assessment Primary survey: (i) Airway(ability of air to pass unobstructed to the lungs): critical findings include: - obstruction of the airway due to direct injury, oedema, foreign body or inability to protect the airway because of depressed level of consciousnesss key treatment is: - establishment of airway (ii) Breathing (ability to ventilate and oxygenate): key clinical findings are: - absence of spontaneous ventilation, absent or asymmetrical breath sounds, dyspnoea hyperresonance, dullness, gross chest wall instability or defects that compromise ventilation key conditions to identify are: - pneumothorax, endotracheal tube malposition, tension pneumothorax, haemothorax, sucking chest wounds, flail chest key treatment is: - chest tube (iii) Circulation: key clinical findings are: - collapsed or distended neck veins, signs or tamponade, external sites of haemorrhage key conditions identified are: - hypovolaemia, cardiac tamponade, external haemorrhage key treatment is: - iv access, fluid resuscitation, compression of sites of bleeding (iv) Disability: key clinical conditions are: - decreased level of consciousness, pupillary assymetry, gross weakness key conditions identified are: - serious head and spinal cord injury key treatment is: - definitive airway if indicated, emergency treatment of raised icp (v) Exposure and control of immediate environment: - expose patient and prevent hypothermia Resuscitation phase: - continues throughout primary and secondary survey and until treatments are complete - fluids are required to sustain intravascular volume, tissue and organ perfusion and urine output - administer blood for hypovolaemia that is unresponsive to crystalloid boluses - end points are normal vital signs, absence of blood loss, adequate urine output and no evidence of end organ dysfunction; blood lactate and base deficit on an ABG may be helpful in patients who are severely injured Other procedures: several monitoring and diagnostic adjuncts occur in concert with the primary survey: (i) ECG and ventilatory monitoring and continous pulse oximetry (ii) decompress stomach with NG or OG tube once airway is secured (iii) insert a foley cather during resuscitation phase (foley catheter placement is contraindicated if urethral injury is evident as identified by blood at the meatus, ecchymosis or scrotum or labium majora or high riding prostate - retrograde urethrogram is required for these patients) Secondary survey of abdominal trauma: (i) inspection: - examine for the presence of external signs of injury noting patterns of abrasion and/or ecchymotic areas - lap belt bruising is positively correlated with rupture of the small intestine and increased incidence of other intraabdominal injury (20-30% of patients with lap-belt marks have associated mesenteric or intestinal injuries) - bradycardia may indicate free intraperitoneal blood - Cullen sign (periumbillical ecchymosis) may indicate retroperitoneal haemorrhage; however, this usually takes hours to develop - flank bruising and swelling may raise suspicion for retroperitoneal injury - inspect genitals and peritoneum (ii) palpation: - fullness may indicate haemorrhage - crepitation of lower rib cage may indicate hepatic or splenic injury - rectal and vaginal examination identify potential bleeding and injury - signs of peritonitis soon after injury suggest leakage of intestinal contents; peritonitis due to intra-abdominal haemorrhage may take several hours to develop FAST: - used to identify free fluid in the peritoneal cavity - FAST has a sensitivity of 70-95% - involves directing to ultrasound probe in four regions: (i) the subxipoid location to determine whether there is fluid in the pericardial space & to make a rough assessment of contractility & filling state (ii) the right upper quadrant (iii) the splenorenal recess (iv) the pelvis - problems with FAST: (i) operator dependent (ii) false negative rate in children is high (iii) technically more difficult with obesity & sc empysema CT abdo/pelvis: - is the diagnostic modality of choice for haemodynamically stable patients - the major reason not to obtain a CT scan is haemodynamic instability - allows haemoperitoneum & its source to be identified & allows specific injuries to be graded - CT also permits evaluation of retroperitoneal structures including the kidneys, major blood vessels & bony pelvis - the majority of blunt solid organ injuries are now managed non-operatively in trauma centres; however, a blush of intravenous contrast agent indicates active extravasation from a bleeding vessel and is strong predictor of failure of non-operative management - problems with CT scanning are: (i) the need to transfer the patient to radiology (ii) the time associated with transfer and scanning (iii) risks associated with intravenous contrast agents (iv) the fact hollow viscus, diaphragmatic & pancreatic injuries are frequently missed on initial scanning abdominal trauma consists of blunt and penetrating trauma Penetrating abdominal trauma: - most commonly injured organs with stab wounds are small intestine, liver and colon - only one third of abdominal stab wounds penetrate the peritoneum & only 50% of these require surgical intervention - 85% of abdominal wall gun shot wounds penetrate the peritoneum & 95% of these require a surgical procedure for correction Blunt abdominal trauma - spleen and liver are the most commonly injured organs; small and large intestines are the next most commonly injured DPL: - has an accuracy of 98% for detection of haemoperitoneum but does not determine source - generally performed in patients too unstable for CT - involves performing a minilaparotomy with placement of a lavage catheter into the periotoneal cavity directed towards the pelvis - the return of gross blood is a positive result - if DPL is grossly negative then 1L of warmed saline is instilled into the the abdominal cavity & then drained back into the intravenous fluid bag by gravity. The effluent lavage is sent to the laboratory for analysis. - laboratory criteria for a positive DPL in blunt trauma are: (i) >100000 RBCs/mm3 (ii) >500 WBC/mm3 (iii) presence of food particles (iv) presence of bile (v) presence of bacteria - problems with DPL: (i) an invasive procedure (ii) 1/4 of patients with a positive DPL will have a non-therapeutic laparotomy (iii) 5% false negative rate with retroperitoneal, hollow viscus or diaphragm injuries - ongoing haemorrhage is the most likely cause of persistent or recurrent haemodynamic instability - initial goal is not to diagnose specific abdominal organ injury but rather to determine wheter there are signs & symptoms that indicate a need for immediate laparotomy 30% of patients with lumbar Chance fracture have associated bowel or mesenteric injuries criteria for positive DPL
3. 3. abdo USS cholecystitis obstructed renal tract duplex scan kidneys FAST post liver transplant duplex USS
4. 4. AXR bowel obstruction volvulus toxic megacolon gastric dilatation extraluminal air calcifications ascites gallstone ileus fractures devices organomegally duodenal obstruction
5. 5. abnormal ventilator waveforms auto-PEEP alveolar overdistension cardiac oscillations circuit leaks Normally, expiratory flow returns to the baseline prior to the next breath. In the event that the expiratory flow does not return to the zero line and the subsequent inspiration begins below the baseline, auto-PEEP or air trapping is present. The presence of auto-PEEP or air trapping may result from: a. Inadequate expiratory time b. Too high a respiratory rate c. Long Inspiratory Time d. Prolonged exhalation due to bronchoconstriction. - The classic sign, known as "Beak Effect" or "Duckbill" shows an increase in airway pressure without any appreciable increase in volume. baseline of the pressure-time waveform shows slight up and down movements with heartbeat; these may initiate triggering of synchronised breaths increased airway resistance & decreased lung compliance Normal curve: - demonstrates normal PIP , Pplat , PTA (transairway pressure), and Ti (inspiratory time). High Raw: - A significant increase in the PTA is associated with increased in airway resistance. High Flow: - the inspiratory time is shorter than normal, indicating a higher inspiratory gas flow rate. Decreased Lung Compliance: - An increase in the plateau pressure and a corresponding increase in the PIP is consistent with decreased lung compliance. inadequate inspiratory flow - inadequate inspiratory flow rate on the pressure time waveform leads to a 'scooped out' appearance to the synchronised breaths there is less volume expired than inspired baseline of the pressure time waveform drifts downwards
6. 6. acidosis in kidney disease [created by Paul 15/12/07] Distal (Type 1) Renal Tubular Acidosis General - This is also referred to as classic RTA or distal RTA. - The problem here is an inability to maximally acidify the urine. Typically urine pH remains > 5.5 despite severe acidaemia ([HCO3] < 15 mmol/l). - Some patients with less severe acidosis require acid loading tests (eg with NH4Cl) to assist in the diagnosis. If the acid load drops the plasma [HCO3] but the urine pH remains > 5.5, this establishes the diagnosis. General Classification of Causes of type 1 RTA (i)Hereditary (genetic) (ii) Autoimminue diseases (eg Sjogren's syndrome, SLE, thyroiditis) (iii) Disorders which cause nephrocalcinosis (eg primary hyperparathyroidism, vitamin D intoxication) (iv) Drugs or toxins (eg amphotericin B, toluene inhalation) (v) Miscellaneous - other renal disorders (eg obstructive uropathy) Pathophysiological Mechanisms in Reduced H+ Secretion in Distal Tubule (i) "Weak pump" - Inability for H+ pump to pump against a high H+ gradient (ii) "Leaky membrane" - Back-diffusion of H+ [eg This occurs in RTA due amphotericin B] (iii) "Low pump capacity" - Insufficient distal H+ pumping capacity due to tubular damage. Investigation - Typical findings are an inappropriately high urine pH (usually > 5.5), low acid secretion and urinary bicarbonate excretion despite severe acidosis. Renal sodium wasting is common and results in depletion of ECF volume and secondary hyperaldosteronism with increased loss of K+ in the urine. - The diagnosis of type 1 RTA is suggested by finding a hyperchloraemic acidosis in association with an alkaline urine particularly if there is evidence of renal stone formation. Note: If [HCO3 > 15 mmol/l, then acid loading tests are required to establish the diagnosis. Treatment - Treatment with NaHCO3 corrects the Na+ deficit, restores the extracellular fluid volume and results in correction of the hypokalaemia. Typical alkali requirements are in the range of 1 to 4 mmol/kg/day. K+ supplements are only rarely required. Sodium and potassium citrate solutions can be useful particularly if hypokalaemia is present. Citrate will bind Ca++ in the urine and this assists in preventing renal stones. Proximal (Type 2) Renal Tubular Acidosis General - Type 2 RTA is also called proximal RTA because the main problem is greatly impaired reabsorption of bicarbonate in the proximal tubule. - At normal plasma [HCO3], more than 15% of the filtered HCO3 load is excreted in the urine. When acidosis is severe and HCO3 levels are low (eg 10 mOsm/l is often stated to be abnormal. Importance of the type of osmometer - Only osmometers using freezing point depression method should be used for determining this calculation because they are the only type of osmometer that can detect all the volatile alcohols which can abnormally increase the osmolar gap. Vapour pressure osmometers can't do this Significance of an elevated osmolar gap - An elevated osmolar gap provides indirect evidence for the presence of an abnormal solute which is present in significant amounts. To have much effect on the osmolar gap, the substance needs to have a low molecular weight and be uncharged so it can be present in a form and in a concentration (measured in mmol/l) sufficient to elevate the osmolar gap. - Ethanol, methanol & ethylene glycol are three such solutes that, when present in appreciable amounts, will cause an elevated osmolar gap. If you suspect that your patient may have ingested one of these substances than you should determine the osmolar gap. - if the ethanol levels are measured they can be added to the calculated osmolarity to exclude the presence of an additional contributer to the osmolar gap. [NB: To convert ethanol levels in mg/dl to mmol/l divide by 4.6. For example, an ethanol level of 0.05% is 50mg/dl. Divide by 4.6 gives 10.9mmols/l] delta ratio Definition - The Delta Ratio is sometimes useful in the assessment of metabolic acidosis. - The Delta Ratio is defined as: Delta ratio = (Increase in Anion Gap / Decrease in bicarbonate) Use - In order to understand this, consider the following: - If one molecule of metabolic acid (HA) is added to the ECF and dissociates, the one H+ released will react with one molecule of HCO3- to produce CO2 and H2O. This is the process of buffering. The net effect will be an increase in unmeasured anions by the one acid anion A- (ie anion gap increases by one) and a decrease in the bicarbonate by one. - if all the acid dissociated in the ECF and all the buffering was by bicarbonate, then the increase in the AG should be equal to the decrease in bicarbonate so the ratio between these two changes (which we call the delta ratio) should be equal to one. The delta ratio quantifies the relationship between the changes in these two quantities. - the above assumptions about all buffering occurring in the ECF and being totally by bicarbonate are not correct. Fifty to sixty percent of the buffering for a metabolic acidosis occurs intracellularly. This amount of H+ from the metabolic acid (HA) does not react with extracellular HCO3- so the extracellular [HCO3-] will not fall as far as originally predicted. The acid anion (ie A-) however is charged and tends to stay extracellularly so the increase in the anion gap in the plasma will tend to be as much as predicted. - Overall, this significant intracellular buffering with extracellular retention of the unmeasured acid anion will cause the value of the delta ratio to be greater than one in a high AG metabolic acidosis. Sources of error: - Inaccuracies can occur for several reasons, for example: (i) Calculation requires measurement of 4 electrolytes, each with a measurement error (ii) Changes are assessed against 'standard' normal values for both anion gap and bicarbonate concentration. Assessment < 0.4 - Hyperchloraemic normal anion gap acidosis - A low ratio occurs with hyperchloraemic normal anion gap acidosis. The reason here is that the acid involved is effectively hydrochloric acid (HCl) and the rise in plasma [chloride] is accounted for in the calculation of anion gap (ie chloride is a 'measured anion'). - The result is that the 'rise in anion gap' (the numerator in the delta ration calculation) does not occur but the 'decrease in bicarbonate' (the denominator) does rise in numerical value. - The net of of both these changes then is to cause a marked drop in delta ratio, commonly to < 0.4 0.4 - 0.8 - Consider combined high AG & normal AG acidosis BUT note that the ratio is often 2 - A high delta ratio can occur in the situation where the patient had quite an elevated bicarbonate value at the onset of the metabolic acidosis. Such an elevated level could be due to a pre-existing metabolic alkalosis, or to compensation for a pre-existing respiratory acidosis (ie compensated chronic respiratory acidosis). anion gap General: - The term anion gap (AG) represents the concentration of all the unmeasured anions in the plasma. The negatively charged proteins account for about 10% of plasma anions and make up the majority of the unmeasured anion represented by the anion gap under normal circumstances. - the AG = [Na+] + [K+] - [Cl-] - [HCO3-] and a the upper range of normal is about 15 Major Clinical Uses of the Anion Gap (i) To signal the presence of a metabolic acidosis and confirm other findings - If the AG is greater than 30 mmol/l, than it invariably means that a metabolic acidosis is present. If the AG is in the range 20 to 29 mmol/l, than about one third of these patients will not have a metabolic acidosis. (ii) Help differentiate between causes of a metabolic acidosis: -high anion gap versus normal anion gap metabolic acidosis. The effect of albumin & phosphate - Albumin is the major unmeasured anion and contributes almost the whole of the value of the anion gap. - Every one gram decrease in albumin will decrease anion gap by 2.5 to 3 mmoles. A normally high anion gap acidosis in a patient with hypoalbuminaemia may appear as a normal anion gap acidosis. - This is particularly relevant in Intensive Care patients where lower albumin levels are common. - the 'normal anion gap depends on the serum phosphate and the serum albumin. anion gap = 0.2 x [albumin] (g/L) + 1.5 x [phosphate] (mmol/L) metabolic acidosis with increased anion gap: Methanol, metformin Uraemia DKA Phenformin, paraldehyde, propylene glycol, pyroglutamic acidosis Iron, isoniazid Lactic acidosis Ethanol ketoacidosis, ethylene glycol Salicylates, starvation ketoacidosis, solvent metabolic acidosis with normal anion gap: Ureteroenterostomy (K+ decreased) Small bowel fistula (K+ decreased) Extra chloride (K+ increased) Diarrhoea (K+ decreased) Carbonic anhydrase (K+ decreased) Renal tubular acidosis (K+ decreased - type 1) Addison's disease (K+ increased) Pancreatic fistula (K+ decreased)
7. 13. adjunctive respiratory therapies general - Most critically ill patients are unable to effectively clear secretions that accumulate in the central and peripheral airways. This can be due to factors such as: (i) increased secretion production, (ii) impaired cough reflex, (iii) weakness, and (iv) pain. - Adjunctive respiratory therapy addresses many of these concerns to prevent and treat respiratory complications that are encountered in the critically ill patient. general techniques methods to improve mucociliary clearance 1. Percussion: - percussion of the chest can aid in secretion clearance. - It is performed by clapping cupped hands over regions of the thorax that are affected in a rhythmic fashion or using mechanical devices that mimic the same action. 2. High-frequency chest compression (HFCC): - relies on rapid pressure changes to the respiratory system during expiration to enhance movement of mucus in the peripheral airways to the central airways for clearance. This method employs a vest worn by the patient that is attached to an air-pulse generator. It is difficult to apply this technique to most critically ill patients because the size of the vest covering the thorax may prevent adequate monitoring. 3. Manual hyperinflation - Typically, the lungs are inflated slowly to one and one-half to two times the tidal volume or peak airway pressures of 40 cm H2O as measured by a manometer. - It is held at end inspiration with an inspiratory pause to allow for filling of alveoli with slow time constants. - The goal of manual hyperinflation is to recruit atelectatic lung regions to improve oxygenation and improve clearance of secretions. - Contraindications include hemodynamic compromise and high intracranial pressure. - There is also a risk of barotrauma because of preferential inflation of open lung regions that are highly compliant compared with collapsed regions. 4. Positioning & mobilization: - Mobilization of patients in the ICU either through active or passive limb exercises may improve overall patient well-being and in the long term may lead to better patient outcomes. - Positioning also plays an important role. Position of the patient with the head of the bed elevated at least 30 degrees significantly reduces the risk of aspiration and ventilator- associated pneumonia. - Positioning of selected individuals with unilateral lung disease on their side with the affected side up can lead to improved ventilation-perfusion matching (by gravitational increased perfusion to the dependent "good" side). - If atelectasis secondary to retained secretions is the cause, having the affected side up leads to postural drainage. 5. tracheal suction - Used in conjunction with other techniques to mobilize secretions from the peripheral airways to the central airways, suctioning is an effective way of removing secretions to improve bronchial hygiene. - Because of the anatomic arrangement of the large central airways, the suction catheter most often enters the right mainstem bronchus compared with the left mainstem bronchus. - Complications with suctioning include hypoxemia, especially in the setting of a ventilator disconnect, increased intracranial pressure with vigorous stimulation of the airways, mechanical trauma to the trachea, and bacterial contamination. - All patients should be preoxygenated with 100% oxygen for 1 to 2 minutes before suctioning. - To reduce the risk of agitation, the patient should be informed before tracheal suctioning is performed. The suctioning should be limited to 15 to 20 seconds. The suction port on the catheter should be opened and closed intermittently and not closed for more than 5 seconds at a time. 6. Continuous rotational therapy - extends the practice of regular 2 hourly repositioning of patients from one side to the other by placing the patient on a bed that moves to pre-programmed angles on a more frequent basis or through the use of air mattresses that deflate alternatively from side to side to provide the continuous postural position changes. - Most studies on various patient populations demonstrate a lower incidence of nosocomial pneumonia or atelectasis but no overall improvement in other clinically significant outcomes such as duration of mechanical ventilation, length of stay in the ICU, or mortality. 7. Assisted coughing - Techniques include "huffing" in the setting of an open glottis where in expiration the patient forcibly exhales quickly several times. Other maneuvers include abdominal or thoracic compression on expiration to generate high intrathoracic pressures mimicking a cough. 8. Positive expiratory pressure therapy (PEP) - involves the use of a facemask or mouthpiece that provides a resistance to airflow of 10 to 20 cm H2O on expiration. After repeating this maneuver a number of times, mucus in the peripheral airways is mobilized and moved toward the larger airways to be coughed or expelled with other techniques. 9. Bronchoscopy - Fiberoptic bronchoscopy has the advantage of providing direct visualization of the airways and permits suctioning of specific segments where secretions may be retained, causing problems such as atelectasis. - Bronchoscopy can be considered as an adjunctive therapy for the treatment of atelectasis or removal of secretions. - Being an invasive procedure, bronchoscopy is not without risks, including complications associated with sedation required for the procedure, transient increases in ICP, hypoxemia, and hemodynamic consequences/arrhythmias. methods to improve lung expansion - Atelectasis is a common complication encountered in the critically ill patient. This is often secondary to prolonged supine body position and retained secretions obstructing airways. - Lung expansion techniques mimic normal sigh maneuvers to help reverse and prevent atelectasis and include: (i) Deep breathing and incentive spirometry (ii) Intermittent positive-pressure breathing aerosol therapies general: - The aerosolization of medications is an effective method for drug delivery directly to lungs. The two most common methods of delivery are via nebulization or via metered- dose inhalers (MDIs). - The theoretical advantage of this form of therapy includes direct delivery and activity at the site of pathology and the ability to deliver high concentrations with minimal systemic absorption and toxicity. - The most common aerosolized therapy is the administration of bronchodilators. Other medications that can be administered directly to the lungs include corticosteroids, antibiotics, antifungal agents, surfactant, mucolytic agents, and saline. (i) Nebulization: - the process of using a high flow of gas (usually 6 to 8 L/min) to produce small respirable particles of the liquid medium containing the medication of interest. - in the spontaneously breathing patient approximately 10% reaches the lower respiratory tract/small airways. In mechanically ventilated patients, 1% to 15% is delivered to the lower respiratory tract. (ii) MDIs - pressurized canisters with the drug suspended in a mix of propellants, preservatives, and surfactants. - Factors that influence the efficacy of aerosol delivery in the mechanically ventilated patient include: 1. Position of administration in the circuit: the MDI should be closer to the endotracheal tube at the Y-piece with a chamber, compared with a pneumatic nebulizer, which should be at least 30 cm from the Y-piece. 2. Humidification: this can decrease aerosol delivery to the respiratory tract because of greater deposition in the ventilator circuit. Higher doses may be required to achieve the desired effect. 3. Timing of delivery: the aerosol should be delivered during the inspiratory phase to maximize drug delivery. 4. Flow rates: slower inspiratory flow rates (and therefore longer inspiratory time) increase delivery of nebulized medications. A decelerating flow pattern can also increase delivery to the lower airways. 5. Tidal volumes: larger tidal volumes greater than 500 mL ensure optimal delivery. 6. Endotracheal tube size: tube sizes less than 7.0 mm reduce delivery. 7. Density of inhaled gas: low-density gases such as helium-oxygen mixtures increase deposition to the lower airways by increasing laminar flow and producing smaller respirable particle size. Bronchodilators: - Bronchodilators are the most frequently administered aerosolized therapy in the critically ill patient and are generally well tolerated in the critically ill patient. - In mechanically ventilated patients, the use of nebulization is either equally as good as or less effective than an MDI with a spacer. MDI administration has the advantage of easier use without the risk of bacterial contamination and need for adjustment of flow rates. Antibiotics - Theoretical advantages of aerosolized antibiotics include direct therapy at the site of infection at higher concentrations with a lower risk of systemic absorption and side effects. - The role for aerosolized or instilled (via the endotracheal tube) antibiotics as an adjuvant for the prevention or treatment of pulmonary infections in the ICU remains to be defined with better clinical studies. Mucoactive agents: - Induce bronchospasm and probably have no role Adrenaline: - Racemic epinephrine has been used as a therapy for acute upper airway obstruction secondary to inflammation
8. 14. adjunctive therapies to improve oxygenation & ventilation properties of NO clinical trials of NO - Numerous clinical observational studies in ALI/ARDS have demonstrated improvements in oxygenation by improving VQ mismatch as demonstrated by a 10% to 20% increase in PaO2/FIO2 ratio and a reduction on pulmonary vascular resistance and mean pulmonary arterial pressures by at least 5 to 8 mm Hg. - Nitric oxide was first described as a vascular-derived relaxing factor that caused vasodilation via vascular smooth muscle relaxation. It is a highly lipid-soluble gas that allows for rapid diffusion through the alveoli-blood barrier into the pulmonary circulation and smooth muscle cells of the vasculature. - The main action of NO is mediated by activating guanylate cyclase and increasing intracellular cyclic guanylate monophosphate, thereby causing smooth muscle and subsequent vasomotor relaxation. - The beneficial effects observed with inhaled NO are mediated primarily through this action on the pulmonary vascular smooth muscle. Pulmonary blood flow is specifically increased in well-ventilated regions, which improves matching of perfusion to ventilation. - It also has anti-inflammatory effects - Randomized controlled trials of varying sample size and design had similar findings. Typically, NO improved the PaO2 and PaO2/FIO2 ratios acutely, but by 24 to 72 hours those in the control group achieved the same level of improvement. - Similarly, although a reduction in mean pulmonary artery pressure was also observed in these trials with the use of NO, this did not translate into clinically meaningful outcomes of a decrease in mortality, less organ failure, or days free of mechanical ventilation. - Only 60% of ALI/ARDS patients respond to inhaled NO. No clear predictors of who will respond to NO exist. clinical use of nitric oxide - Given that doses below 40 ppm were safe without any significant adverse effects, it can be considered a "rescue" therapy to possibly allow for more protective forms of ventilation with decreases in FIO2 and mean airway pressures to maintain acceptable oxygenation or in situations in which secondary pulmonary hypertension leads to compromised hemodynamic function from right ventricular failure potential indications include: - Inhaled NO is typically started at low doses ranging from 1 to 2 ppm and gradually increased until the desired effect is achieved. - One method, as recommended from the U.K. Consensus conference on NO use, is to perform a dose response test starting at 20 ppm and reducing the doses to 10, 5, and 0 ppm to find the lowest effective dose. A significant response should be considered as a 20% increase in the PaO2/FIO2 ratio or at least a 5 mm Hg decrease in the mean pulmonary artery pressure. - The improvement in gas exchange is usually seen at lower doses. The dose required to reduce mean pulmonary artery pressure is usually higher. The usual dose ranges from 10 to 40 ppm. - Doses greater than 80 ppm are associated with a higher risk for adverse effects. adverse effects of nitric oxide - Adverse effects of NO include: (i) the formation of methemoglobin and (ii) the spontaneous oxidation to nitrogen dioxide (NO2). NO2 is known to be toxic to the respiratory system with maximal exposure limited to 5 ppm. Complications from NO2 exposure include airway irritation and hyperreactivity with levels as low as 1.5 ppm, pulmonary edema, and pulmonary fibrosis when exposed to higher levels. (iii) Rebound pulmonary: vasoconstriction can occur with sudden discontinuation leading to rapid worsening of VQ mismatch and pulmonary hypertension with significant hemodynamic collapse safe administration of nitric oxide - To reduce the risk of exposure to NO2, NO should be stored at concentrations no higher than 1000 ppm in a pure nitrogen environment and only exposed to oxygen at the time of administration. - NO should be delivered into the ventilator circuit as close to the patient as possible. - NO and NO2 levels should be monitored closely on the inspiratory side of the Y-piece when using doses greater than 2 ppm. contraindications to nitric oxide - An absolute contraindication to NO therapy is methemoglobinemia reductase deficiency (congenital or acquired). - Relative contraindications include bleeding diathesis (secondary to reports of alteration in platelet function and bleeding time with inhaled NO), intracranial hemorrhage, and severe left ventricular failure (New York Heart Association grade III or IV). inhaled prostaglandins - Inhaled prostaglandins I2 (PGI2) and E1 (PGE1) are alternative medications that have effects similar to inhaled nitric oxide with minimal systemic effects. - For PGI2, doses ranging from 1 to 25 ng/kg/min are favorably tolerated with similar reductions in pulmonary artery pressures and improvements in oxygenation as inhaled NO. - PGE1 has the advantage of a more rapid degradation by the pulmonary endothelial cells, providing a selective advantage over PGI2 at higher doses. - Additional studies are required to define a role for these agents, but they can be considered as alternatives for rescue therapy for similar conditions treated with inhaled NO. heliox - Helium is an inert gas with a significantly lower density than room air (1.42 g/L for oxygen versus 0.17 g/L for helium). - By substituting helium for nitrogen in a helium-oxygen mix (heliox), the degree of reduction in density of the gas is directly proportional to the fraction of the inspired helium concentration in the mix. - Heliox reduces the Reynolds number and thereby results in more laminar flow, therefore reducing airflow resistance, work of breathing, and dynamic hyperinflation associated with a high resistance. - Clinical situations in which heliox may be used include conditions with high airflow resistance such as severe acute exacerbations of asthma or COPD, bronchiolitis, bronchopulmonary dysplasia, and extrathoracic or tracheal obstruction. - Disadvantages of using heliox in critically ill patients include the cost of therapy and the high concentrations of helium required. Most studies utilize helium:oxygen mixes of 80:20 or 70:30 to achieve a therapeutic benefit. At higher concentrations of oxygen, the effect of helium is less and therefore is limited in use to those not requiring high FIO2. Ventilators also require recalibration for measured FIO2, flows, and tidal volumes when using heliox.
9. 15. adrenal insufficiency in sepsis & septic shock [created by Paul Young 10/12/07] guidelines - international guidelines recommend the use of low dose corticosteroids for the treatment of septic shock. However, there are some discrepancies in these recommendations. (i) the Surviving Sepsis Campaign recommended the use of stress dose of corticosteroids for septic shock regardless of adrenal function. (ii) the American College of Critical Care Medicine Task Force recommended that stress dose of corticosteroids should be used only in refractory septic shock or in adrenal insufficient patients. mechanisms of action of corticosteroids genomic actions - Cells from most tissues are responsive to corticosteroids, which freely cross cell membranes. The glucocorticoids receptor forms an inactive intracytosolic complex with chaperone proteins like heat shock protein (HSP) 40, HSP56, HSP70, and HSP90, immunophillins, P23, and other unknown proteins - The receptor contains three domains: one binds corticosteroids, one binds to DNA, also involved in dimerization; and one activates the promoters within the genes. - Binding of corticosteroids to the glucocorticoids receptor induces the release of chaperone proteins and the dimerization of the complex, which then, enters into the nucleus and interacts with specific binding sequences, the glucocorticoid responsive element (GRE). - Subsequently, transcription of some genes (e.g.most cytokines, adhesionmolecules, lipoxygenase, etc.) initiated by various transcriptional factors such as AP1, NF-AT and NF-kB are prevented. In addition, glucocorticoids receptor dimers induce the inhibitor of NFkB (IkB). - Other GRE sites upregulate the transcription of numerous other genes (e.g. lipocortin-1, thymosin-b4 sulfoxide). Nongenomic interactions - Physicochemical interactions occur in-between the cell's membrane and corticosteroids inducing very rapid (within seconds), nonspecific, nongenomic effects. - Some of these effects might be part of the host response to sepsis. For example, loss in the corticosteroids physicochemical interaction with hypothalamic synaptosomes], may partly explain the loss in circadian rhythm of cortisol synthesis during sepsis. - non genomic effects of cortisol are thought to control immediate catecholamine release from sympathetic cells. Such neural modulation by corticosteroids may explain the rapid restoration of sympathetic modulation on heart and vessels, and may account for the hydrocortisone induced rapid pressure sensitization to exogenous catecholamine in septic shock. corticosteroid induced immune modulation - by interacting with NF-IL6, corticosteroids enhance the synthesis of the acute phase reactants; with AP-1 and NF-kB, they inhibit the synthesis of various proinflammatory factors. - corticosteroids prevent the migration of inflammatory cells from circulation to tissues by blocking the synthesis of various chemokines and chemotactic cytokines. They prevent the synthesis of almost all proinflammatory cytokines including several interleukins (interleukin-1, interleukin-2, interleukin-3, interleukin-6), interferon-g (IFN- g), granulocyte macrophage colony stimulating factor, and tumor necrosis factor-a (TNF- a). They also enhance the production of the macrophage migration inhibitory factor (MIF). - by stimulating the synthesis of lipocortin-1, corticosteroids inhibit the synthesis of soluble phospholipase A2 (PLA2) and the subsequent arachidonic acid cascade, reducing the production of leukotrienes, the main inflammatory mediators in humans. - corticosteroids also inhibit the synthesis of inducible cyclooxygenase-2 (COX2) and of inducible but not constitutive nitric oxide synthase (NOS). corticosteroid induced cardiovascular modulation - Chronic corticosteroid excess induces hypertension, whereas adrenal insufficiency induces hypotension. - corticosteroids regulate vascular responses to norepinephrine and angiotensin II, but not to vasopressin. The underlying mechanisms remained unclear, and may involve multiple pathways like iNOS and COX-2 inhibitions or the stimulation of the phosphoinositide system. human studies - in healthy volunteers, a 6-hour infusion of 3 mg/kg/min hydrocortisone, either immediately before or concomitantly to endotoxin exposure, prevented LPS-induced fever, tachycardia, increase in plasma levels of epinephrine, CRP, and TNF-a, but not interleukin-6. conclusion - In septic shock, intravenous hydrocortisone (about 300 mg for 5 days) decreases core temperature, heart rate, and plasma levels of PLA2 and C-reactive protein. - In a French multicenter trial on low dose corticosteroids in septic shock, it was shown that the systemic inflammatory response to sepsis, assessed by interleukin-6 levels, was significantly altered by corticosteroids only in adrenal insufficient patients - nonresponders (increment in cortisol of 9 mg/dl or less) to 250 mg of corticotropin. In that study, the adrenal insufficient septic shock had higher TNFa, interleukin-6 and interleukin-8 levels than the remainders. - In another placebo-controlled, randomized trial, 41 patients with septic shock received 50mg bolus followed by a continuous infusion of 0.18 mg/kg/h of hydrocortisone until shock reversal. In that study, as compared with the placebo, interleukin-6 levels were also significantly decreased by hydrocortisone infusion, whereas interleukin-10 levels remained unaltered. - low dose of hydrocortisone has been shown to downregulate sepsis-associated overexpression of the 'late' inflammatory mediator, MIF by peripheral blood monocytes - In a recent randomized study, the acute vascular effects of hydrocortisone (200 mg intra-arterial over 3 hours) were investigated in healthy adult male volunteers. This study elegantly demonstrated that hydrocortisone did not affect biochemical or physiologic markers of nitric oxide activity. Thus, one can conclude that any early (within 3 h) vascular effect of hydrocortisone is not mediated through the NO pathway. - In septic shock, several placebo-controlled randomized studies have reported the cardiovascular effects of low dose of corticosteroids (about 200-300 mg/day) given for a prolonged period. These studies consistently showed that corticosteroids increased systemic vascular resistance with little effects on the cardiac index and pulmonary hemodynamics. - trials consistently show that corticosteroids reduce the duration of shock. The probability of being weaned from vasopressor at one week was greater in corticosteroid- treated septic shock than in placebo-treated septic shock and the relative risk was 1.60 - Only three trials have subgroup analyses based on adrenal insufficiency. However, only two studies used the same definition for adrenal insufficiency. In both of them, the favorable effects of corticosteroids on shock reversal were observed only in the adrenal insufficient patients (nonresponders to corticotropin). - In the first study of 300 patients with septic shock, the median time to weaning from vasopressors was reduced by 3 days in the corticosteroid-treated adrenal insufficient patients compared with the placebo group (P = 0.001), while there were no difference between corticosteroids and placebo in the responders to corticotropin. In the second study, hydrocortisone significantly shortened the duration of shock (P = 0.02). This effect was seen only in the adrenal insufficient septic shock (n=26; P=0.06), and not in the responders to corticotropin (n = 15; P = 0.90). - Confalonieri et al. have investigated the efficacy and safety of a 7-day treatment with intravenous hydrocortisone (240 mg/day) in community-acquired pneumonia associated sepsis. In their study, treatment with hydrocortisone significantly prevented onset of shock (P =0.001), reduced multiple organ dysfunction score (P =0.003), hospital length of stay (P = 0.03), and in-hospital mortality (P = 0.009). - In septic shock, evidence from five randomized trials suggested that prolonged treatment with low dose corticosteroids reduced 28-day mortality (relative risk = 0.80, 95% confidence interval 0.67-0.95), in-hospital mortality (relative risk = 0.83, 95% confidence interval 0.71-0.97), and ICU mortality (relative risk = 0.83, 95% confidence interval 0.70-0.97). It is important, however, to note that one study accounted for 70% of patients included in that meta-analysis. In this study, corticosteroids improved survival only in adrenal insufficient septic shock. - In a meta-analysis of all published randomized trials that evaluated the effects of high or low doses of corticosteroids for short or long periods of time, there was no evidence for significant increases of super-infection, gastroduodenal bleeding, or hyperglycemia. - Corticosteroids could be a valuable treatment for septic shock, depending upon the way they are used. - There is no evidence to support the use of short courses of high doses of corticosteroids in patients with severe sepsis. - Current evidence suggests that, in septic shock, one-week treatment with 200-300 mg of hydrocortisone alleviates the symptoms of systemic inflammatory response, reduces the duration of shock, and increases survival. Corticosteroids favorable effects on inflammation, hemodynamics, and survival are more marked in patients with an increment in cortisol of 9 mg/dl or less after 250 mg of corticotrophin (nonresponders or adrenal insufficient).
10. 16. adrenocortical insufficiency [created by Paul Young 03/12/07] aetiology diagnosis of acute adrenal crisis physiology - The adrenal gland is a mixture of the steroid hormone-producing adrenal cortex and the adrenal medulla, which is responsible for the secretion of catecholamines. - The secretion of cortisol and aldosterone is controlled by different mechanisms, whereby the pituitary axis (corticotropin-releasing hormone [CRH] or corticotropin) is vital for cortisol secretion and the renin-angiotensin system is vital for aldosterone secretion. - Cortisol regulates a wide variety of genes involved in energy metabolism (eg, glucose-protein-fatty acid metabolism), mineral homeostasis, and immune function and influences many more cellular functions. - Aldosterone has a more focused action on mineral homeostasis - Although adrenal insufficiency has been known as a clinical syndrome for a long time, new risk groups have been identified, because as many as 20% of AIDS patients eventually develop adrenal insufficiency. Moreover, patients with head trauma develop pituitary insufficiency much more frequently than previously recognized. symptoms of adrenal insufficiency epidemiology - Primary and secondary adrenal insufficiency (excluding critical illness adrenal insufficiency and adrenal insufficiency secondary to acute interruption of chronic glucocorticoid therapy) are rare diseases, affecting less than 0.1% of the population - usually present slowly over time with nonspecific symptoms of chronic fatigue, weakness and lethargy, anorexia and weight loss, postural hypotension, abdominal complaints (eg, nausea, vomiting, diffuse abdominal pain), and loss of libido as well as loss of axillary and pubic hair in women. - Hyperpigmentation (attributable to excess proopiomelanocortin and melanocyte- stimulating hormone), especially of non-sunlight-exposed skin areas, is an imported clinical hallmark for the attentive and suspicious physician. - Abnormal serum electrolytes with low sodium, high potassium, and, occasionally, hypercalcemia and fasting hypoglycemia, and especially this combination are highly suspicious for adrenal insufficiency. - Acute adrenal insufficiency (adrenal crisis) is mainly attributable to mineralocorticoid deficiency; thus, the clinical presentation is dominated by hypotension or hypotensive shock. treatment - If adrenal insufficiency is confirmed or highly likely based on the acute screening results, replacement therapy should be continued by the intravenous or intramuscular route (at 150-300 mg/d for 2 to 3 days) until full clinical recovery. High dose cortisol replacement has major mineralocorticoid effects therefore no additional mineralo- corticoid therapy is needed in the acute phase. - The 150- to 300-mg/d replacement dose of hydrocortisone is frequently considered to be a physiologic stress dosage. However, serum cortisol levels measured after such so- called ''acute replacement'' dosages exceed several times the maximal stress cortisol levels found in healthy or even critically ill patients thereby questioning the need for maintaining such high acute emergency replacement dosages. - In contrast to the rather generous replacement dosage used in emergency situations, the chronic replacement dosage for patients with adrenal insufficiency should be as low as possible with clear instructions for dosage adjustments in case of stress or acute emergencies. - Detailed information about and education of the patient and of his or her family and a medical emergency alert card as well as appropriate follow-up should be initiated. pathophysiology - adrenal insufficiency is a hormone deficiency syndrome attributable to primary adrenal diseases or caused by a wide variety of pituitary-hypothalamic disorders. - if such diseases evolve gradually over time, they rarely cause an abrupt-onset adrenal insufficiency crisis, whereas acute destruction of the adrenal or pituitary gland or acute interruption of glucocorticoid therapy is more likely to cause an acute onset adrenal failure crisis. - there is increasing attention to relative adrenal insufficiency in patients with acute (nonadrenal or pituitary) critical illness. Such patients still secrete cortisol (and corticotropin in the early phases of critical illness) but less than expected during acute stress, and the survival of such patients can be improved by pharmacologic doses of glucocorticoids.