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C H A P T E R 57 Drug Overdoses and Toxic Ingestions Pia Chatterjee n Jeanmarie Perrone Successful management of patients after a life-threatening drug overdose depends on emergency medical system (EMS) and emergency department (ED) personnel (1) initiating the critical interventions of airway management and cardiovascular stabilization, (2) simultaneously obtaining a thorough history, and (3) targeting specific therapies based on the suspected exposure Communication between the ED and the intensive care unit (ICU) will be paramount for continuing successful resuscitations in the ICU Not all “drug overdoses” are intentional Toxic ingestions may be accidental or result from the ingestion of products stored inappropriately—for example, lye stored in a soda bottle Iatrogenic dosing errors and excess self-medication of drugs with narrow therapeutic:toxic ratios (salicylates, lithium, digoxin) also occur Occasionally, chronic medications precipitate acute toxicity caused by a drug interaction or a change in drug metabolism Acute management of poisoned patients will depend on the ingestion; however, disposition of patients following ICU care depends on whether or not the overdose was intentional Although deep sedation and coma in patients admitted to the ICU may be attributed to a drug ingestion, patients with unclear histories should undergo evaluation for other causes of altered mental status Intracranial pathologic conditions should be excluded by computed tomographic (CT) scan of the head, and lumbar puncture should be considered in febrile patients The regional poison center is an additional important resource in the management of any suspected poisoning, including those resulting from “new” recreational drugs with serious toxic side effects, such as “bath salts” or synthetic cannabinoids (“K2/Spice”), and new therapies including use of lipid therapy for hemodynamically significant poisonings Mechanisms of Injury DIRECT DRUG EFFECTS Nearly all drugs produce harmful effects if taken in excessive amounts Systemic toxicity is due to selective effects of the toxin or a metabolite on specific targets, such as binding to specific receptors (therapeutic drugs), disruption of metabolic pathways (cyanide, salicylates, iron), cellular production of toxic metabolites (acetaminophen in the liver, methanol in the retina, ethylene glycol in the kidney), and enzymatic inhibition (Na+/K+-ATPase by digoxin; anticholinesterase by organophosphates) Some toxins produce effects by several mechanisms For example, isoniazid causes both hepatotoxicity via a cytochrome P-450 pathway metabolite and neurotoxicity via the inhibition of pyridoxal 5′-phosphate Pathologic effects may also occur at the site of exposure as a result of cytotoxic chemical reactions (e.g., caustic acid or alkali ingestions) that damage exposed tissue 557 558 5—PRESENTING PROBLEMS FOR INTENSIVE CARE UNIT ADMISSION COMPLICATIONS Aspiration occurs in poisoned patients as a complication of vomiting, orogastric lavage, endotracheal intubation, or loss of airway reflexes because of obtundation Early assessment and definitive airway management are critical in diminishing the risk of aspiration Acute lung injury may complicate recovery following life-threatening ingestions Hyperthermia may occur for several reasons: increased motor activity that occurs with agitation or seizures, direct drug effects on the hypothalamus (sympathomimetics), or aspiration and pneumonia Rhabdomyolysis (see Chapter 81) can occur in patients after prolonged periods of immobilization because of obtundation, protracted agitation or seizures, or cocaine or amphetamine use Under these circumstances, aggressive hydration and maintenance of urine output are important Acute renal failure (see Chapter 81) may occur directly, for example, from ethylene glycol direct toxic effects on the kidneys or secondarily, for example, from drug-induced hypotension Acute hepatic failure (see Chapter 59) most commonly results from acetaminophen poisoning but may also occur because of the multiorgan effects of diffuse toxins such as mercury or iron Management DIAGNOSTIC APPROACH Initial assessment of the airway, breathing, and circulatory status (ABCs) and frequent reassessment are critical to monitoring the dynamic status of ongoing toxicity Empty pill bottles or discussions with family members regarding medicines available in the home are helpful in focusing the diagnostic workup Physical examination should screen for manifestations of common toxic syndromes (“toxidromes”)—for example, anticholinergic, opioid, or salicylate toxicity An electrocardiogram can screen for conduction defects associated with cyclic antidepressants, calcium channel antagonists, beta-blockers, or digoxin QR and QT prolongation herald impending cardiotoxicity and should be followed serially Toxicology screening should be performed if the results will be available in a sufficiently short time frame to be clinically relevant All patients with intentional ingestions should have an acetaminophen level checked to exclude a clinically silent, potentially overlooked but treatable acetaminophen ingestion THERAPEUTIC APPROACH After initial stabilization of the ABCs, certain therapies should be considered in all poisoned patients Suspected hypoglycemia should be treated with an intravenous (IV) bolus of concentrated dextrose solution (50 mL of 50% dextrose) Patients with the triad of signs suggesting opioid toxicity (respiratory depression, pinpoint pupils, and coma) warrant treatment with the opioid antagonist naloxone IV fluid therapy is important in many patients with overdoses to compensate for volume losses associated with vomiting Parenteral benzodiazepine sedation is indicated for agitated or uncooperative patients because it may prevent rhabdomyolysis, hyperthermia, and injuries to the patient or staff as well as decrease the risk of seizures Gastrointestinal (GI) decontamination is no longer routinely recommended for most overdose patients but may have a limited role in some patients with serious toxicity admitted to the ICU Orogastric lavage via a large-bore tube (Ewald tube) may be critical in patients ingesting large quantities of drugs not bound by activated charcoal, such as iron or lithium It can be life saving in serious calcium channel antagonist overdoses by removing a clinically significant fraction of drug, decreasing toxicity Orogastric lavage should only be considered in patients manifesting signs of toxicity following a potentially life-threatening ingestion, and only perform it after the judging the patient’s airway to be protected, often necessitating endotracheal intubation 57—DRUG OVERDOSES AND TOXIC INGESTIONS 559 TABLE 57.1 n Antidotes and Adjuncts in the Therapy of Selected Poisonings Toxin Antidote Dosing for Adults and Comments Acetaminophen N-acetylcysteine Anticholinergic agents Physostigmine Beta-adrenergic antagonists Calcium channel blockers Glucagon Orally 140 mg/kg × 1; followed by 70 mg/kg every hours × 17 doses IV: 150 mg/kg IV over 60 minutes, followed by an infusion of 12.5 mg/kg/h over a 4-hour period, and finally an infusion of 6.25 mg/kg/h over a 16-hour period 1–2 mg IV over minutes; use with caution for severe delirium (may cause seizures, bronchospasm, asystole, cholinergic crisis) 2–5 mg IV; titrate repeat doses; may use infusion of 2–10 mg/h g (10 mL of 10% solution) IV over minutes with electrocardiographic monitoring; repeat as needed, check serum calcium after third dose Bolus dose of 0.1 U/kg followed by an infusion of 0.5 mg/kg/h; can be titrated up to a rate of U/kg/h with a dextrose infusion to maintain euglycemia 1–2 mEq/kg IV; titrate to arterial pH of 7.5 or electrocardiographic alterations (see text) Vials (number) = (digoxin level [ng/mL] × weight [kg])/100 or 10–20 vials for a life-threatening arrhythmia Loading dose of 15 mg/kg IV over 30 minutes; subsequent doses every 12 hours at 10 mg/kg; further dosing per poison center 0.05–0.4 mg IV, repeat as needed; infusion: two thirds of reversal dose/h, titrate to effect Calcium gluconate Insulin Cyclic antidepressants Digoxin Sodium bicarbonate Methanol Ethylene glycol Fomepizole Opioids Naloxone Digoxin antibodies (Digibind) Oral activated charcoal can diminish the absorption of many drugs and can enhance drug excretion for some agents via GI dialysis (the diffusion of high plasma drug levels back into the gut lumen to be bound to activated charcoal and excreted) or interruption of enterohepatic circulation of active metabolites Sustained release preparations (e.g., calcium channel blockers) and drugs not bound to activated charcoal (e.g., lithium, iron) may be cleared from the gut using whole bowel irrigation Bowel irrigation is performed with polyethylene glycol–electrolyte lavage solutions (e.g., GoLYTELY, CoLYTE) administered via nasogastric tube at a rate of to L/h in adults The regional poison control center should be consulted to obtain general management and toxin-specific therapeutic advice, as many common toxins have specific therapies or antidotes (Table 57.1) Common Toxic Ingestions ACETAMINOPHEN Acetaminophen is one of the most commonly ingested medications Few patients become seriously ill from acetaminophen overdose because of early diagnosis and antidote treatment with N-acetylcysteine (NAC) Life-threatening hepatotoxicity, however, occurs in the few who present late after their ingestions or in whom clinicians fail to recognize acetaminophen when it is coingested with other drugs 560 5—PRESENTING PROBLEMS FOR INTENSIVE CARE UNIT ADMISSION Patients with a history of acetaminophen ingestion should have a > 4-hour post ingestion acetaminophen level obtained and interpreted using the Rumack-Matthew nomogram (Figure 57.1) Nausea, vomiting, and sometimes right upper quadrant abdominal pain are associated with toxic hepatitis from ingestions a day or two earlier Patients with jaundice or coagulopathy or those reporting a large acetaminophen ingestion to days previously should be presumed to have hepatotoxicity and should have treatment initiated immediately When presentations are delayed more than 24 hours after ingestion, acetaminophen levels may be low or zero, but significant elevations in transaminases and prothrombin time reflect severe acetaminophen poisoning Therapeutic doses of acetaminophen are metabolized in the liver by glucuronidation (60%), sulfation (30%), or by the P-450 cytochrome oxidase system (4%) The last pathway results in a toxic intermediate, N-acetyl-p-benzoquinoneamine (NAPQI) NAPQI is then normally reduced by glutathione, which prevents toxicity With increasing dose or overdose, more acetaminophen metabolism is shunted into the P-450 system, depleting glutathione As a result, NAPQI accumulates and induces centrilobular necrosis of the liver The antidote NAC replenishes the glutathione and prevents hepatic necrosis (Chapter 59) Patients with toxic acetaminophen levels require a loading dose of NAC (140 mg/kg) and subsequent dosing every hours (70 mg/kg) for an additional 17 doses over 72 hours NAC can also be given parenterally with a loading dose of 150 mg/kg IV over 60 minutes then by continuous Figure 57.1 The Rumack-Matthew nomogram (solid line) estimates the likelihood of hepatotoxicity in acute acetaminophen overdose N-acetylcysteine (NAC) therapy is recommended if the acetaminophen plasma level at hours (or later) after ingestion plots above the broken line For example, patients with levels greater than or equal to approximately 150 μg/mL at hours or greater than or equal to approximately 35 μg/mL at 12 hours after ingestion should be treated with NAC (see text) The broken line allows a 25% variability below the solid line to take into account inaccuracies in estimated time of ingestion or measurement of plasma level (Adapted from Rumack BH, Matthew H: Acetaminophen poisoning and toxicity Pediatrics 44:871-876, 1975.) 57—DRUG OVERDOSES AND TOXIC INGESTIONS 561 IV infusion over 20 hours (see Table 57.1) Although most effective within the first hours after overdose, NAC therapy is effective up to 24 hours after overdose as well as in patients with fulminant hepatic failure secondary to acetaminophen The current recommended dose and route of administration (orally versus IV) in these situations can be obtained via the local poison center NAC should be continued until the acetaminophen level is zero and the liver function tests are trending down ALCOHOLS The clinical effects of ethanol intoxication can range from giddiness to coma and is affected by time and quantity ingested, tolerance, and co-ingestants When presented with patients with presumed ethanol-induced altered mental status, although debated in the literature, measurement of ethanol levels may confirm the clinical correlation as well as prevent inappropriate assumptions that high ethanol levels are the etiology of the altered mental status in any one patient The initial evaluation of any patient acutely intoxicated with alcohol should address whether significant co-ingestants may be present and add to impending morbidity Such considerations include ingestion of other central nervous system (CNS) depressants that may add to eventual respiratory depression such as benzodiazepines or other sedatives, as well as the ingestion of toxic alcohols as ethanol substitutes The toxic alcohols to consider include methanol, ethylene glycol, and isopropanol Methanol is found in Sterno, windshield washer fluids, and industrial solvents Ethylene glycol is the principal ingredient in most antifreeze preparations and is also used in deicing agents Isopropanol is commonly used as rubbing alcohol and as a solvent in home products These substances are readily available to ingest as an alcohol substitute in patients who are made abstinent from alcohol or, in other cases, secondary to suicidal intention The presence of an anion gap acidosis in a patient with suspected ethanol intoxication should promote a diagnostic search for the presence of methanol or ethylene glycol The findings of an osmolar gap or anion gap acidosis can be helpful when making the diagnosis but must be interpreted with caution depending on the time since ingestion and the amount of metabolism that may have occurred Soon after ingestion, either ethanol or a toxic alcohol will cause an elevated osmolar gap because all alcohols are osmotically active Over several hours, this osmolar gap will diminish, whereas an anion gap acidosis will develop if methanol or ethylene glycol were ingested instead of ethanol These toxic alcohols will undergo metabolism to an organic acid (formic acid in methanol poisoning and glycolic acid and oxalic acid in ethylene glycol poisoning) This acidosis, as well as the exclusion of other causes of metabolic acidosis (lactic acid, salicylate ingestion), helps confirm the suspicion of toxic alcohol ingestion while confirmatory methanol and ethylene glycol levels are obtained Other clinical symptoms that suggest toxic alcohol ingestion are alcohol specific Methanol exposure is characterized by visual symptoms that develop within 12 to 24 hours of exposure Patients complain of “snow field” vision that occurs from formic acid–mediated retinal toxicity Ethylene glycol may cause acute tubular necrosis and acute renal failure 12 to 48 hours after ingestion because of calcium oxalate precipitants in the kidneys The principal toxicity of isopropanol ingestion is CNS depression, lethargy, and coma as well as ketosis but not a metabolic acidosis because isopropanol is metabolized to acetone contributing to an osmolar gap but not an anion gap acidosis Laboratory testing should include finger-stick glucose, electrolytes, ethanol level with other alcohols, and serum osmolarity Urine fluorescence with a Wood’s lamp can detect the presence of antifreeze (and presumably ethylene glycol) shortly after ingestion; however, this finding is not always present An electrocardiogram (EKG) may show QT prolongation secondary to hypocalcemia from calcium oxalate precipitation in the kidneys 562 5—PRESENTING PROBLEMS FOR INTENSIVE CARE UNIT ADMISSION Fomepizole, like ethanol, blocks metabolism of the toxic alcohols by competitively inhibiting the enzyme alcohol dehydrogenase and is the recommended treatment for suspected ethylene glycol and methanol poisoning When available, fomepizole is preferred to an ethanol infusion because it does not require following serum ethanol levels and increases safety by not adding synergistic respiratory depression Hemodialysis still has a role in toxic alcohol ingestions and should be discussed with the nephrology team Traditional indications for hemodialysis include severe acidosis, renal failure, or inability to obtain fomepizole or ethanol therapy If an elevated level of ethylene glycol or methanol is discovered, administer fomepizole, but if an acidosis is not yet present, some patients can be managed expectantly with fomepizole and not dialysis CALCIUM CHANNEL AND BETA-ADRENERGIC ANTAGONISTS Accidental or intentional ingestion of the potent calcium channel blockers or beta-adrenergic antagonists can result in significant morbidity and fatalities Patients present with bradycardia and hypotension The mental status may be normal or reflect obtundation, seizures, or coma following beta-blocker poisoning, and it typically remains normal despite significant hypotension in the setting of calcium channel blocker poisoning Poisoning with these drugs must be considered in any young person with unexplained bradycardia and may be misdiagnosed as a complicated myocardial infarction or conduction defect in older patients Sustained release preparations may produce delayed onset of toxicity and profound decompensation may occur after a period of relative stability Because beta-adrenergic antagonists decrease intracellular cyclic adenosine monophosphate, a specific therapeutic role has been demonstrated for the hormone glucagon Glucagon increases myocardial cyclic adenosine monophosphate via a non–beta-adrenergic receptor mediated mechanism Following a trial of atropine, glucagon should be given (3 to 10 mg IV bolus followed by a to mg/h IV infusion) Calcium channel antagonists block slow inward calcium channels on vascular smooth muscle and myocardial cells, causing conduction defects, negative inotropic and chronotropic effects, and peripheral vasodilation Intravenous calcium competitively antagonizes these effects and may work synergistically with atropine and catecholamine pressors Norepinephrine, as an alpha and beta agonist, antagonizes both the negative inotropic effects as well as the peripheral vasodilation that are concomitantly contributing to hypotension The use of hyperinsulinemic euglycemic therapy has demonstrated efficacy in moribund calcium channel antagonist poisoned patients Following acute management and stabilization, GI decontamination must address the sustained release preparations and their potential for prolonged toxicity Appropriate management includes orogastric lavage, activated charcoal administration, and whole bowel irrigation Therapy for bradycardia begins with atropine (0.5 to mg IV bolus), followed by 10% calcium chloride or calcium gluconate Calcium therapy may be repeated to a total dose up to several grams if there is a clinical response High-dose insulin infusion has been described as a novel treatment for calcium channel poisoning Insulin has several proposed mechanisms of action including increasing plasma levels of ionized calcium, improving myocardial utilization of carbohydrates, and a positive inotropic effect Insulin therapy can be initiated with a bolus dose of 0.1 U/kg followed by an infusion of 0.5 mg/kg/h This infusion can be titrated up to a rate of U/kg/h, with a dextrose infusion to maintain euglycemia In isolated cases with massive ingestion and poor response to pharmacologic therapy, placement of a transvenous pacer, an intra-aortic balloon pump and extracorporeal membrane oxygenation (ECMO) have each been successful COCAINE Cocaine is a potent sympathomimetic drug commonly abused either by nasal insufflation of cocaine hydrochloride or smoked in the form of “crack” cocaine Cocaine readily crosses the 57—DRUG OVERDOSES AND TOXIC INGESTIONS 563 blood-brain barrier and has a rapid onset of action Patients with acute intoxication may complain of chest pain or agitation and may be hypertensive, tachycardic, hyperthermic, and agitated Seizures are not uncommon Pulmonary toxicity may result in bronchospasm, pneumothorax, or pneumomediastinum as well as diffuse alveolar hemorrhage “Crack lung” is the combination of diffuse alveolar infiltrates, eosinophilia, and fevers Upper airway injuries can occur secondary to thermal effects including uvulitis and epiglottitis Wide complex dysrhythmias occur secondary to QRS and QT prolongation mediated by sodium channel blockade comparable to types IA and IC antidysrhythmic drugs Case reports have illustrated successful treatment with sodium bicarbonate therapy Rhabdomyolysis is also common, and a creatine phosphokinase (CPK) level should be checked and trended Treatment of acute overdose includes supportive care, rapid cooling for hyperthermia, and benzodiazepines for treatment of seizures and agitation Special consideration should be given to body stuffers and body packers Body stuffers tend to ingest drugs hastily because of a fear of arrest Body packers ingest large quantities of drugs that are carefully packaged for drug trafficking and face greater potential toxicity in the presence of package leakage or rupture The onset of altered mental status, seizures, or hypertension heralds rapid absorption of “pure” cocaine, and emergent surgery for gut decontamination is indicated Asymptomatic body packers can be identified by abdominal radiographs or contrast abdominal computed tomography (CT) scans Asymptomatic body stuffers and packers should be given multiple doses of activated charcoal to decrease potential cocaine absorption followed by whole bowel irrigation for body packers until all of the packets have been passed A follow-up contrast study can help confirm that the gut has been cleared of retained packets OPIOIDS: HEROIN, FENTANYL, AND METHADONE Heroin overdoses are a frequent cause of EMS calls as well as ED visits requiring the opioid antagonist naloxone to reverse life-threatening respiratory depression When faced with the triad of respiratory depression, pinpoint pupils, and lethargy or coma, the administration of small doses of naloxone starting at 0.05 to 0.4 mg IV will induce reversal of respiratory depression and can be followed by larger doses if a desired response (arousal, increased respirations) occurs Caution should be used in patients deemed opioid tolerant such as heroin users or chronic pain patients in that abrupt reversal may precipitate withdrawal (vomiting, agitation) and in some cases may not improve mental status when other CNS depressants (alcohol, benzodiazepines) are co-ingested Thus, vomiting can occur while the patient remains sedated and aspiration can result Long-acting opioids such as methadone or sustained release morphine or oxycodone may result in recurrent opioid toxicity In these cases, a continuous naloxone infusion can be initiated because a bolus dose of naloxone will not sustain reversal relative to the longer duration of action of the opioid These patients will need ICU admission and should be observed for recurrent toxicity for a period after the naloxone infusion is stopped Patients who are unresponsive and cyanotic after an opioid overdose and then revived with naloxone are at some risk for acute lung injury Dyspnea may develop within a few minutes to few hours, and a chest radiograph will show pulmonary edema This can be treated with supplemental oxygen, non-invasive ventilation (Chapter 3), or, rarely, intubation DIGOXIN Although the mortality rate of digoxin poisoning has dramatically improved with the use of digoxin-specific antibody fragments (Digibind), both acute and chronic digoxin poisoning continues to occur Patients with acute digoxin poisoning may present with emesis and brady- or tachydysrhythmias Chronic digoxin toxicity often occurs when a patient develops a decrease in renal function, decreasing digoxin clearance by the kidneys GI symptoms are less prominent, and, instead, slight changes in mental status and visual disturbances as well as bradycardia may occur 564 5—PRESENTING PROBLEMS FOR INTENSIVE CARE UNIT ADMISSION Following acute stabilization of a patient with potential digoxin toxicity, oral-activated charcoal should be administered Immediate serum potassium and digoxin levels should be obtained and electrocardiographic monitoring should be initiated Bradycardia, conduction defects, ventricular ectopy, bidirectional ventricular tachycardia, and atrial tachycardia or atrial fibrillation (but without rapid ventricular response) may be seen with digoxin poisoning Any dysrhythmia is an indication for Digibind therapy If Digibind is not immediately available, atropine can be given for bradycardia Potassium elevations > mEq/L indicate significant toxicity and reflect digoxin-induced inhibition of the Na+/K+-ATPase pump This is used as a surrogate marker for toxicity, and treatment with Digibind is indicated as well In the setting of an unknown overdose with bradycardia when the differential diagnosis includes calcium channel blockers, beta-blockers, and digoxin, patients should be treated with Digibind before they are treated with calcium because calcium can significantly and sometimes lethally exacerbate digoxin poisoning ORAGANOPHOSPHATES Organophosphates are commonly used as insecticides, include diazinon, malathion, parathion and chlorpyrifos Exposures can occur from occupational exposure in agriculture or military use in chemical warfare Organophosphates bind irreversibly to inhibit the enzyme acetylcholinesterase, thereby increasing acetylcholine at nerve synapses and overstimulating the nicotinic and muscarinic receptors Clinical presentation depends on the specific agent, dose, and route of exposure Poisoned patients present with CNS effects ranging from restlessness to delirium, coma, and seizures The classic cholinergic toxidrome includes salivation, lacrimation, diaphoresis, urinary incontinence, emesis, and bradycardia An intermediate syndrome can occur to days after an exposure that presents with muscle weakness without cholinergic findings The diagnosis of organophosphate poisoning depends on the clinical symptoms and history Usually, serum tests are not available in a clinically relevant time frame Treatment consists of airway control, supportive measures and decontamination These patients have excessive airway secretions and bronchospasm and may require endotracheal intubation Use only nondepolarizing neuromuscular antagonists (such as rocuronium) to prevent prolonged paralysis Atropine, a competitive antagonist of acetylcholine, is used to reverse the excessive cholinergic state The dose is titrated to drying of bronchial secretions, and large doses may be necessary Atropine will not reverse muscle weakness Following atropine therapy, consider pralidoxime as an adjunct therapy in severe organophosphate poisoning PSYCHOTROPIC MEDICATIONS Cyclic Antidepressants Cyclic antidepressants continue to produce significant toxicity in overdose Screen all overdose patients by electrocardiography for possible cyclic antidepressant ingestion Prolongation of QRS duration (> 100 msec) is associated with serious toxicity In one early study, one third of patients with QRS duration > 100 msec had a seizure, and half of those with a QRS greater than 160 msec had a dysrhythmia A positive deflection of the R wave in lead aVR and an S wave in leads I and aVL are also clues to the presence of a cyclic antidepressant Patients with cyclic antidepressant ingestions may present with lethargy and anticholinergic signs such as tachycardia, dry mouth, dilated pupils, decreased bowel sounds, and urinary retention Seizures, dysrhythmias, or both signify serious cyclic antidepressant ingestion Patients with recent ingestions (within the prior 30 to 90 minutes) may be asymptomatic initially but rapidly deteriorate in the first hour in the emergency department Initiate orogastric lavage and activated charcoal early Obtundation often mandates endotracheal intubation If the QRS is > 100 msec, give a trial 57—DRUG OVERDOSES AND TOXIC INGESTIONS 565 of sodium bicarbonate (IV bolus followed by infusion) with a goal of alkalinization of the serum to pH 7.45 to 7.55 Alkalinization decreases drug binding to the myocardium, expands the plasma volume, and overcomes the sodium channel blocking type IA cardiotoxic effects induced by the cyclic antidepressant Use benzodiazepines to treat seizures because a resultant lactic acidosis will exacerbate the cardiotoxicity If hypotension persists despite sodium bicarbonate and other fluid therapy, a direct vasoconstrictor such as norepinephrine will be more effective than indirectly acting vasopressors Lithium Lithium toxicity differs from other psychotropic drug toxicity Acute lithium ingestions produce considerable vomiting and diarrhea As dehydration ensues, renal lithium excretion decreases because lithium, a cation, is reabsorbed with sodium in the proximal tubule Measure lithium levels, serum electrolytes, and renal function Because lithium does not bind to activated charcoal, consider orogastric lavage for recent ingestions, followed by whole bowel irrigation to limit distal GI absorption Vigorous volume expansion with normal saline enhances lithium excretion Although sodium polystyrene sulfonate (SPS), Kayexalate, has been proposed as a binder of lithium, concerns about inducing hypokalemia limit its use Patients on chronic lithium therapy can become ill with elevated lithium levels after a new medication (especially diuretics) or an intercurrent GI illness induces dehydration and a change in renal lithium clearance The principal toxicity of lithium is to the CNS in both acute and chronic exposures Patients with acute ingestions will have some GI symptoms initially, followed by neuromuscular manifestations such as hyperreflexia, fasciculations, choreoathetosis, nystagmus, clonus, and lethargy to coma as toxicity progresses Acute ingestions manifest elevated serum levels, reflecting rapid absorption yet slow distribution to intracellular compartments and the CNS Therefore, patients may initially be asymptomatic despite high serum levels During this time, lithium is most accessible to dialysis Any patient with lithium levels > mEq/L should undergo hemodialysis, as renal elimination is insufficient to prevent significant neural accumulation of lithium Any patient with serious neurologic symptoms (altered mental status, seizures, or coma) from lithium should also undergo hemodialysis A lithium level immediately after hemodialysis and hours later should be measured because some patients may need a second treatment after lithium redistributes into the serum from the intracellular space Unfortunately, not all patients with elevated levels and neurologic signs recover fully, even with hemodialysis SALICYLATES Salicylates are commonly found in many over-the-counter analgesics and combination cold preparations Other agents such as methyl salicylate (oil of wintergreen), liniments, and products used for vapor rubs all contain salicylates Acute salicylate toxicity often manifests with vomiting and auditory disturbances (tinnitus, hearing loss) Hyperpnea or tachypnea may contribute to the classic mixed acid-base disturbance of a primary respiratory alkalosis and a metabolic acidosis (Chapter 83) Severe hyperthermia and diaphoresis may occur Agitation or confusion may occur and progress to seizures with higher salicylate levels A serum salicylate level should be obtained early and followed serially to determine the extent and course of the ingestion GI decontamination of salicylate-poisoned patients may include orogastric lavage, but most can be effectively treated with multiple doses of activated charcoal Urinary alkalinization should be performed in any symptomatic patient until the salicylate level is less than 30 to 40 mg/dL Alkalinization effectively traps the salicylate ion away from the CNS and preserves 566 5—PRESENTING PROBLEMS FOR INTENSIVE CARE UNIT ADMISSION availability for renal excretion Adding three ampules of sodium bicarbonate (44 mEq/ampule) to L of 5% dextrose in water (D5W) infused IV at a rate of 200 to 300 mL/h alkalinizes the urine Hypokalemia commonly complicates alkalinization and should be corrected prior to initiating Because salicylate poisoning is commonly accompanied by fluid losses (vomiting, sweating, tachypnea), the saline load is usually well tolerated However, cerebral edema and salicylate-induced acute lung injury may complicate alkalinization therapy, especially in elderly patients In general, levels > 100 mg/dL mandate hemodialysis Rapidly rising levels, severe acid-base disturbances, neurologic complications, or volume overload precluding alkalinization may also require hemodialysis Early consultation with a nephrologist is advisable in any significant salicylate poisoning SEDATIVES Benzodiazepines Benzodiazepines are a surprisingly safe drug for sedation, causing dose-dependent CNS depression Unlike barbiturates, however, first-generation benzodiazepines (diazepam, chlordiazepoxide) have only rarely been associated with significant respiratory or cardiovascular depression However, all benzodiazepines may produce life-threatening CNS and respiratory depression when ingested along with large amounts of ethanol or other sedative-hypnotic agents As with barbiturates, benzodiazepine dependence is also common, and withdrawal may present as a severe delirium tremens–like syndrome Laboratory testing by qualitative immunoassay is widely available Many rapid screens use oxazepam as the immunoreagent, and therefore some of the newer benzodiazepines that are not metabolized to oxazepam go undetected Management of benzodiazepine toxicity is supportive, with no proven benefit for enhanced elimination The role of a specific antagonist, flumazenil, in overdose management is controversial Because its effect is brief (1 to hours) and its use may precipitate seizures (in a benzodiazepine-dependent patient or with concomitant cocaine or cyclic antidepressant ingestion), avoid flumazenil in patients admitted to the ICU GHB (γ-Hydroxybutyrate) γ-Hydroxybutyrate (GHB) has been used as an anesthetic, a therapy for narcolepsy, and a treatment for ethanol and opioid withdrawal; however, it has also been abused as a recreational drug GHB is usually abused in the setting of dance parties or nightclubs After ingestion, GHB is rapidly absorbed and acts in the CNS at gamma aminobutyric acid (GABA) and opioid receptors The hallmark of poisoning is deep sedation, followed by unusually fast resolution to normal mental status Significant respiratory depression may require ventilatory support; modest bradycardia is often present Myoclonic motion of the face and extremities is sometimes noted Reversal agents such as naloxone and flumazenil are not effective Treatment is supportive, and patients usually recover within a few hours without sequelae SEROTONERGIC AGENTS Serotonin syndrome (SS) is a complication of serotonergic agents, which are most commonly available as the newer, safer antidepressants and increase serotonin in the CNS Although SS may occur after an overdose of such an agent, more often SS occurs soon after an increase in dose of a primary serotonergic agent or the addition of a second agent Serotonergic drugs are legion, including selective serotonin reuptake inhibitors, such as fluoxetine, tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, amphetamines such as “Ecstasy” (3,4-methylenedioxymethamphetamine or MDMA), and opioids such as meperidine, tramadol, and dextromethorphan 988 APPENDIX B—TIDAL VOLUME RATIOS (VD/VT) Notes: 30 1) VCO2 = VA × 2) VE = Minute ventilation (VE) (L/min BTPS) 25 PaCO2 PB VA · 310 · 310 273 273 V I– D VT Assume VCO2 = 200 mL/min 20 C 15 Dead space/ tidal volume ratio (VD/VT) B 0.85 A 10 0.75 0.66 0.60 0.50 0.40 0.30 0.15 20 30 40 50 60 70 80 Arterial CO2 tension (mm Hg) Figure B2 For example, consider a patient with chronic obstructive pulmonary disease (COPD) and chronic CO2 retention who has a baseline Paco2 of 50 mm Hg and who has just been intubated and started on mechanical ventilation for acute or chronic respiratory failure With the ventilation delivering 10 L/min of V˙ E (assuming that the patient’s respiratory rate is the set rate on the ventilator), an arterial blood gas indicates that the patient’s Paco2 equals 70 mm Hg This corresponds to the isopleth with Vd/Vt of 0.75 (point A; such elevated Vd/Vt’s are typical of acute flares of COPD) To decrease his Paco2 to his baseline, 50 mm Hg (but not overshoot which might result in a severe alkalemia), follow the 0.75 isopleth to where it intersects 50 mm Hg (point B) and find that the corresponding V˙ E is 15 L/min Thus, increasing the ventilator’s rate to achieve 15 L/min of V˙ E should result in a Paco2 of ∼50 mm Hg Do not increase the tidal volume to increase V˙ E , as that would change Vd/Vt (and invalidate the assumption of keeping the Vd/Vt the same) If the patient’s Vd/Vt decreases to 0.66 because of increased set tidal volumes, acute treatment for COPD (see Chapter 76), or both, the same V˙ E of 15 L/min will decrease the patient’s Paco2 to slightly below 40 mm Hg and possibly put the patient at risk for a severe alkalemia (point C) Note that one can use Equation in Chapter to arrive at the same result (From Selecky PA, Wasserman K, Klein M, Ziment I: A graphic approach to assessing interrelationships among minute ventilation, arterial carbon dioxide tension and the ratio of physiologic dead space to tidal volume in patients on respirators Am Rev Respir Dis 177:181-184, 1978.) A P P E N D I X C Palliative Drug Therapy for Terminal Withdrawal of Mechanical Ventilation Joshua B Kayser n Tanya J Uritsky n Paul N Lanken TABLE C.1 n Stepwise Approach to Palliative Drug Therapy for Terminal Withdrawal of Mechanical Ventilation Step Step Step Step Step Step Step Step Select agents to be used and route of administration In general, one should use a combination of opioid and benzodiazepine because of their complementary pharmacologic effects: opioid to control air hunger and pain and benzodiazepine to sedate and to control anxiety In order to rapidly titrate their doses to the desired effect, the agents, in general, should be given as intravenous (IV) bolus injections followed by continuous IV infusions If the patient is receiving a neuromuscular blocking agent, stop its administration Allow its effects to wear off or reverse the effects if possible (see Chapter 6) prior to extubation or start of terminal weaning Anticipate that additional opioid or sedative will be needed for palliation after withdrawal of mechanical ventilation (i.e., preemptive dosing) In this case, at least 30 minutes before extubation or start of terminal weaning, give an IV bolus of the agent followed by continuous IV infusion The IV infusion rate should be a certain fraction of the last bolus dosage given, depending on the agent chosen (See Tables C.E1 to C.E6.) If no additional opioid or sedative is judged to be needed before withdrawal from assisted ventilation, continue current level of palliative drug therapy and proceed to step Titrate the dose of agent (steps and 6) to desired effect Adequacy of palliation can be judged by the appropriate level of sedation (e.g., a Richmond Agitation-Sedation Scale [RASS] of –3 to –5; see Chapter 5) and lack of signs or symptoms of pain, anxiety, fear, dyspnea, tachypnea (e.g., respiratory rate < 25/min), or other discomfort Whenever additional doses are given, document in the medical record that the dose was given in order to control specific signs and symptoms of distress, that is, it was being titrated to (the appropriate palliative) effect It is often helpful to the bedside caregivers to be specific in one’s medical orders to hold additional boluses if the patient’s respirations are less than a certain minimal rate (e.g., 10/min; see step 10) If desired effect is not achieved within 15 min, repeat IV bolus of drug at double the dosage of the prior bolus and increase the rate of the continuous infusion by 25% See step 10 if this results in a respiratory rate < 10/min If desired effect is still not achieved, repeat step If using a combination of an opioid and benzodiazepine, alternate between each agent when repeating step When desired effect is achieved, continue the IV infusion at the same rate and extubate the patient or begin the terminal wean Reassess level of palliation and responsiveness, using signs listed in step 4, every 15 (or at shorter or longer intervals as the clinical condition of the patient dictates) Continued on the following page 989 990 APPENDIX C—PALLIATIVE DRUG THERAPY FOR TERMINAL WITHDRAWAL TABLE C.1 n Stepwise Approach to Palliative Drug Therapy for Terminal Withdrawal of Mechanical Ventilation—cont’d Step Step 10 If the patient exhibits discomfort, repeat bolus at double the dosage of the most recent bolus and increase the rate of the continuous infusion by 25% If discomfort persists, repeat this step until desired effect is again achieved Administer doses based on the frequency described in step If the respiratory rate falls below 10/min, continue at the same IV infusion rate but not give more boluses or increase the IV infusion rate unless the patient is clearly in pain or distress Anticipate that the family may misinterpret agonal respirations as representing patient discomfort and prepare them accordingly (see Chapters 102 and 105 for suggested communication skills) If the patient’s blood pressure or pulse falls, not decrease dose or rate but continue as indicated in steps through From Marr L, Weissman DE: Withdrawal of ventilator support from the dying adult patient J Support Oncol 2:283-288, 2004 See online resources for guidelines for dosing for the following agents: morphine, fentanyl, hydromorphone, lorazepam, midazolam, and diazepam APPENDIX C—PALLIATIVE DRUG THERAPY FOR TERMINAL WITHDRAWAL 990.e1 TABLE C.E1 n Morphine Sulfate Dosing for Terminal Withdrawal from Mechanical Ventilation Exposure to Agent over Prior 24 h* Bolus Dosing Continuous Intravenous (IV) Infusion 0–10 mg/h Immediately after the bolus, start a continuous IV infusion at 50% of the bolus dose per hour Appropriate solutions can be made up by dissolving 150 mg of morphine sulfate in 150 mL normal saline or 5% dextrose solution, yielding a concentration of mg/mL If the patient requires reboluses, increase the drip by 25% after each bolus (see steps 4–9, Table C.1) > 10 mg/h *Mean If patient is not at desired level of palliation (see step 4, Table C.1), give 5–10 mg IV “push” at least 30 before extubation or start of terminal wean After 15 min, if desired level of palliation has not been achieved, double the prior dosage and give as a repeat bolus Repeat step as needed until desired end point of symptom control is reached (see steps 4–9, Table C.1) If step is reached, consider using combination therapy with a benzodiazepine as described in Table C.1 If patient is not at desired level of palliation (see step 4, Table C.1), double the maximal hourly dose of morphine administered in the prior 24 h and give it as an IV bolus After 15 min, if desired level of palliation has not been achieved, double the prior dosage and give as a repeat bolus Repeat step as needed until desired end point of symptom control is reached (see steps 4–9, Table C.1) If step is reached, consider using combination therapy with a benzodiazepine as described in Table C.1 Immediately after the bolus, start a continuous IV infusion at 50% of the bolus dose per hour Appropriate solutions can be made up by dissolving 250 mg of morphine sulfate in 250 mL normal saline or 5% dextrose solution, yielding a concentration of mg/mL If the patient requires reboluses, increase the drip by 25% after each bolus (see steps 4–9, Table C.1) hourly dose over prior 24 hours From Truog RD, Campbell ML, Curtis JR, et al: Recommendations for end-of-life care in the intensive care unit: a consensus statement by the American College of Critical Care Medicine Crit Care Med 36:953-963, 2008; Marr L, Weissman DE: Withdrawal of ventilator support from the dying adult patient J Support Oncol 2004;2:283-288; Von Gunton C, Weissman DE: Symptom Control for Ventilator Withdrawal in the Dying Patient, 2nd ed Fast Facts and Concepts July 2005; 34, available at www.eperc.mcw.edu, accessed February 2012; Kompanje EJO, van der Hoven B, Bakker J: Anticipation of distress after discontinuation of mechanical ventilation in the ICU at the end of life Intensive Care Med 34:1593-1599, 2008 990.e2 APPENDIX C—PALLIATIVE DRUG THERAPY FOR TERMINAL WITHDRAWAL TABLE C.E2 n Fentanyl Dosing for Terminal Withdrawal from Mechanical Ventilation Exposure to Agent over Prior 24 h* Bolus Dosing 0–100 μg/h If patient is not at desired level of palliation (see step 4, Table C.1), give 100–200 μg IV “push” (as described in Table C.E1) Refer to steps 4–9 of Table C.1 for continued symptom management > 100 μg/h If patient is not at desired level of palliation (see step 4, Table C.1), double (2×) the maximal hourly dose of fentanyl administered in the prior 24 h and give it as an IV bolus (as described in Table C.E1) Refer to steps 4–9 of Table C.1 for continued symptom management *Mean Continuous Intravenous (IV) Infusion Immediately after the bolus, start a continuous IV infusion at 50% of the bolus dose per hour Appropriate solutions can be made up by dissolving mg of fentanyl in 250 mL normal saline or 5% dextrose solution, yielding a concentration of 16 μg/mL Refer to steps 4–9 of Table C.1 for continued symptom management Immediately after the bolus, start a continuous IV infusion at 50% of the bolus dose per hour Appropriate solutions can be made up by dissolving mg of fentanyl in 250 mL normal saline or 5% dextrose solution, yielding a concentration of 16 μg/ mL If desired, fentanyl can be made up at higher concentrations: 20 μg/mL (5 mg in 250 mL), 50 μg/mL (12.5 mg in 250 mL), 100 μg/mL (25 mg in 250 mL) Refer to steps 4–9 of Table C.1 for continued symptom management hourly dose over prior 24 hours From Truog RD, Campbell ML, Curtis JR, et al: Recommendations for end-of-life care in the intensive care unit: a consensus statement by the American College of Critical Care Medicine Crit Care Med 36:953-963, 2008 APPENDIX C—PALLIATIVE DRUG THERAPY FOR TERMINAL WITHDRAWAL 990.e3 TABLE C.E3 n Hydromorphone Dosing for Terminal Withdrawal from Mechanical Ventilation Exposure to Agent over Prior 24 h* Bolus Dosing 0–2 mg/h > mg/h *Mean If patient is not at desired level of palliation (see step 4, Table C.1), give 1–2 mg IV “push” at least 30 before extubation or start of terminal wean After 15 min, if desired level of palliation has not been achieved, double the prior dosage and give as a repeat bolus Repeat step as needed until desired end point of symptom control is reached (see steps 4–9, Table C.1) If step is reached, consider using combination therapy with a benzodiazepine as described in Table C.1 If patient is not at desired level of palliation (see step 4, Table C.1), double the maximal hourly dose of hydromorphone administered in the prior 24 h and give it as an IV bolus After 15 min, if desired level of palliation has not been achieved, double the prior dosage and give as a repeat bolus Repeat step as needed until desired end point of symptom control is reached (see steps 4–9, Table C.1) If step is reached, consider using combination therapy with a benzodiazepine as described in Table C.1 Continuous Intravenous (IV) Infusion Immediately after the bolus, start a continuous IV infusion at 50% of the bolus dose per hour Appropriate solutions can be made up by dissolving 150 mg hydromorphone in 150 mL normal saline or 5% dextrose solution, yielding a concentration of mg/mL If the patient requires reboluses, increase the drip by 25% after each bolus (see steps 4–9, Table C.1) Immediately after the bolus, start a continuous IV infusion at 50% of the bolus dose per hour Appropriate solutions can be made up by dissolving 250 mg of hydromorphone in 250 mL normal saline or 5% dextrose solution, yielding a concentration of mg/mL If the patient requires reboluses, increase the drip by 25% after each bolus (see steps 4–9, Table C.1) hourly dose over prior 24 hours From Marr L, Weissman DE: Withdrawal of ventilator support from the dying adult patient J Support Oncol 2:283-288, 2004; Truog RD, Campbell ML, Curtis JR, et al: Recommendations for end-of-life care in the intensive care unit: a consensus statement by the American College of Critical Care Medicine Crit Care Med 36:953-963, 2008 990.e4 APPENDIX C—PALLIATIVE DRUG THERAPY FOR TERMINAL WITHDRAWAL TABLE C.E4 n Lorazepam Dosing for Terminal Withdrawal from Mechanical Ventilation Exposure to Agent over Prior 24 h* Bolus Dosing 0–2 mg/h > mg/h *Mean If patient is not at desired level of palliation (see step 4, Table C.1), give 2–4 mg IV “push” at least 30 before extubation or start of terminal wean After 15 min, if desired level of palliation has not been achieved, double the prior dosage and give as a repeat bolus Repeat step as needed until desired end point of symptom control is reached (see steps 4–9, Table C.1) If step is reached, consider using combination therapy with an opioid as described in Table C.1 If patient is not at desired level of palliation (see step 4, Table C.1), double the maximal hourly dose of lorazepam administered in the past 24 h, and give as an IV bolus After 15 min, if desired level of palliation has not been achieved, double the prior dosage and give as a repeat bolus Repeat step as needed until desired end point of symptom control is reached (see steps 4–9, Table C.1) If step is reached, consider using combination therapy with an opioid as described in Table C.1 Continuous Intravenous (IV) Infusion Immediately after the bolus, start a continuous IV infusion at 50% of the bolus dose per hour Appropriate solutions can be made up by dissolving 100 mg of lorazepam in 250 mL normal saline or 5% dextrose solution, or 200 mg in 500 mL normal saline or 5% dextrose solution, yielding a concentration of 0.4 mg/mL If the patient requires reboluses, increase the drip by 25% after each bolus (see steps 4–9, Table C.1) Immediately after the bolus, start a continuous IV infusion at 50% of the bolus dose per hour Appropriate solutions can be made by dissolving 100 mg of lorazepam in 250 mL normal saline or 5% dextrose solution, or 200 mg in 500 mL normal saline or 5% dextrose solution, yielding a concentration of 0.4 mg/mL If the patient requires reboluses, increase the drip by 25% after each bolus (see steps 4–9, Table C.1) hourly dose over prior 24 hours From Marr L, Weissman DE: Withdrawal of ventilator support from the dying adult patient J Support Oncol 2:283-288, 2004; Truog RD, Campbell ML, Curtis JR, et al: Recommendations for end-of-life care in the intensive care unit: a consensus statement by the American College of Critical Care Medicine Crit Care Med 36:953-963, 2008 Jacobi J, Gilles LF, Coursin DB, et al: Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult Crit Care Med 30:119-141, 2002 APPENDIX C—PALLIATIVE DRUG THERAPY FOR TERMINAL WITHDRAWAL 990.e5 TABLE C.E5 n Midazolam Dosing for Terminal Withdrawal from Mechanical Ventilation Exposure to Agent over Prior 24 h* 0–4 mg/h > mg/h *Mean Bolus Dosing Continuous Intravenous (IV) Infusion If patient is not at desired level of palliation (see step 4, Table C.1), give 2–8 mg IV “push” (as described in Table C.E3).† Refer to steps 4–9 of Table C.1 for continued symptom management Immediately after the bolus, start a continuous IV infusion at 50% of the bolus dose per hour Appropriate solutions can be made up by dissolving 100 mg of midazolam in 100 mL normal saline or 5% dextrose solution, yielding a concentration of mg/mL Refer to steps 4–9 of Table C.1 for continued symptom management If patient is not at desired level of Immediately after the bolus, start a continuous palliation (see step 4, Table C.1), IV infusion at 50% of the bolus dose per double the maximal hourly dose of hour Appropriate solutions can be made up midazolam administered in the past by dissolving 100 mg of midazolam in 100 24 h, and give as an IV bolus mL normal saline or 5% dextrose solution, yielding a concentration of mg/mL Refer to steps 4–9 of Table C.1 for continued symptom management Refer to steps 4–9 of Table C.1 for continued symptom management hourly dose over prior 24 hours starting doses 0.1 to 0.3 mg/kg IV bolus dose But patients who are naïve to benzodiazepines may experience sufficient sedation from a 2-mg dose For patients with prior exposure to midazolam, bolus doses can be initiated at double that of the 24-hour rate From Von Gunton C, Weissman DE: Symptom Control for Ventilator Withdrawal in the Dying Patient, 2nd ed Fast Facts and Concepts July 2005; 34, available at www.eperc.mcw.edu, accessed February 2012; Kompanje EJO, van der Hoven B, Bakker J: Anticipation of distress after discontinuation of mechanical ventilation in the ICU at the end of life Intensive Care Med 34:1593-1599, 2008 †Suggested 990.e6 APPENDIX C—PALLIATIVE DRUG THERAPY FOR TERMINAL WITHDRAWAL TABLE C.E6 n Diazepam Dosing for Terminal Withdrawal from Mechanical Ventilation Exposure to Agent over Prior 24 h* Bolus Dosing 0–60 mg/h > 60 mg *Mean If patient is not at desired level of sedation, give a 10–20 mg IV bolus After 30 min, if desired level of sedation is still not achieved, then give 20–40 mg as an IV bolus If desired effect is seen at 30 postbolus, repeat boluses of same dose q2h Repeat this step until desired end point is reached If patient “breaks through” with signs of discomfort prior to h, repeat steps and and give routine boluses every hour If patient is not at desired level of sedation, give the maximal bolus given over the past h as an IV bolus After 30 min, if desired level of sedation is still not achieved, then double the prior dosage and give as a repeat bolus If desired effect is reached after 30 min, repeat bolus at same dosage at h intervals If patient “breaks through” with signs of discomfort prior to h, repeat steps and and repeat routine boluses every hour Continuous Intravenous (IV) Infusion Diazepam is not recommended for use as a continuous infusion due to the long half-lives of the parent compound and its active metabolite (see Chapter 5) as well as potential for precipitation in IV fluids and absorption of drug into infusion bags and tubing Diazepam is not recommended for use as a continuous infusion due to the long half-lives of the parent compound and its active metabolite (see Chapter 5) as well as potential for precipitation in IV fluids and absorption of drug into infusion bags and tubing hourly dose over prior 24 hours From Jacobi J, Gilles LF, Coursin DB, et al: Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult Crit Care Med 30:119-141, 2002 Roche Pharmaceuticals Valium® (diazepam) injection prescribing information Nutley, NJ; 1999 A P P E N D I X D Advanced Cardiac Life Support (ACLS) Algorithms* American Heart Association ACLS CARDIAC ARREST ALGORITHM Adult Cardiac Arrest Cardiopulmonary Resuscitation (CPR) • Push hard (≥ inches [5 cm]) and fast (≥ 100/min) and allow complete chest recoil • Minimize interruptions in compressions • Avoid excessive ventilation • Rotate compressor every minutes • If no advanced airway, 30:2 compression-ventilation ratio • Quantitative waveform capnography - If PETCO < 10 mm Hg, attempt to improve CPR quality • Intra-arterial pressure - If relaxation phase (diastolic) pressure < 20 mm Hg, attempt to improve CPR quality Shout for help/activate emergency response Start CPR • Give oxygen • Attach monitor/defibrillator Yes No VF/VT Rhythm shockable? Asystole/ PEA Shock Return of Spontaneous Circulation (ROSC) • Pulse and blood pressure • Abrupt sustained increase in PETCO (typically ≥ 40 mm Hg) • Spontaneous arterial pressure waves with intra-arterial monitoring CPR • IV/IO access Rhythm shockable? No Shock Energy • Biphasic: Manufacturer recommendation (e.g., initial dose of 120–200 J); if unknown, use maximum available Second and subsequent doses should be equivalent, and higher doses may be considered • Monophasic: 360 J Yes Shock CPR • Epinephrine every 3–5 • Consider advanced airway, capnography Rhythm shockable? 10 CPR • IV/IO access • Epinephrine every 3–5 • Consider advanced airway, capnography No Rhythm shockable? Yes Advanced Airway • Supraglottic advanced airway or endotracheal intubation • Waveform capnography to confirm and monitor ET tube placement • 8–10 breaths per minute with continuous chest compressions Yes Shock CPR • Amiodarone • Treat reversible causes No 11 CPR • Treat reversible causes No 12 Yes Rhythm • If no signs of return of spontaneous circulation (ROSC), go to 10 or 11 shockable? • If ROSC, go to Post-Cardiac Arrest Care Drug Therapy • Epinephrine IV/IO Dose: mg every 3–5 minutes • Vasopressin IV/IO Dose: 40 units can replace first or second dose of epinephrine • Amiodarone IV/IO Dose: First dose: 300 mg bolus Second dose: 150 mg Go to or Reversible Causes - Hypovolemia - Hypoxia - Hydrogen ion (acidosis) - Hypo-/hyperkalemia - Hypothermia - Tension pneumothorax - Tamponade, cardiac - Toxins - Thrombosis, pulmonary - Thrombosis, coronary Figure D1 Advanced cardiac life support (ACLS) algorithm for ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) ABCs, airway, breathing, and circulation; CPR, cardiopulmonary resuscitation; IV, intravenous; IO, intraosseous; J, joules *Algorithms in Appendix D are from the American Heart Association: Advanced Cardiac Life Support © 1997 American Heart Association, Inc All rights reserved Unauthorized use prohibited 991 992 APPENDIX D—ADVANCED CARDIAC LIFE SUPPORT (ACLS) ALGORITHMS BRADYCARDIA ALGORITHM Adult Bradycardia (With Pulse) Assess appropriateness for clinical condition Heart rate typically < 50/min if bradyarrhythmia Identify and treat underlying cause • Maintain patent airway; assist breathing as necessary • Oxygen (if hypoxemic) • Cardiac monitor to identify rhythm; monitor blood pressure and oximetry • IV access • 12-Lead ECG if available; don’t delay therapy Persistent bradyarrhythmia causing: Monitor and observe No • Hypotension? • Acutely altered mental status? • Signs of shock? • Ischemic chest discomfort? • Acute heart failure? Yes Atropine Doses/Details If atropine ineffective: • Transcutaneous pacing OR • Dopamine infusion OR • Epinephrine infusion Atropine IV Dose: First dose: 0.5 mg bolus Repeat every 3–5 minutes Maximum: mg Epinephrine IV Infusion: 2–10 mcg per minute Consider: Dopamine IV Infusion: 2–10 mcg/kg per minute • Expert consultation • Transvenous pacing Figure D2 ACLS algorithm for treatment of asystole CPR, cardiopulmonary resuscitation; ECG, electrocardiogram; IV, intravenous APPENDIX D—ADVANCED CARDIAC LIFE SUPPORT (ACLS) ALGORITHMS 993 TACHYCARDIA ALGORITHM Adult Tachycardia (With Pulse) Assess appropriateness for clinical condition Heart rate typically ≥ 150/min if tachyarrhythmia Identify and treat underlying cause • Maintain patent airway; assist breathing as necessary • Oxygen (if hypoxemic) • Cardiac monitor to identify rhythm; monitor blood pressure and oximetry Persistent tachyarrhythmia causing: • Hypotension? • Acutely altered mental status? • Signs of shock? • Ischemic chest discomfort? • Acute heart failure? Synchronized cardioversion • Consider sedation • If regular narrow complex, consider adenosine Yes No Wide QRS? ≥ 0.12 second Yes No • IV access and 12-lead ECG if available • Consider adenosine only if regular and monomorphic • Consider antiarrhythmic infusion • Consider expert consultation • IV access and 12-lead ECG if available • Vagal maneuvers • Adenosine (if regular) • β-Blocker or calcium channel blocker • Consider expert consultation Doses/Details Synchronized Cardioversion Antiarrhythmic Infusions for Stable Initial recommended doses: Wide-QRS Tachycardia • Narrow regular: 50–100 J Procainamide IV Dose: • Narrow irregular: 120–200 J biphasic or 20–50 mg/min until arrhythmia suppressed, 200 J monophasic hypotension ensues, QRS duration increases • Wide regular: 100 J > 50%, or maximum dose 17 mg/kg given • Wide irregular: defibrillation dose Maintenance infusion: 1–4 mg/min Avoid (NOT synchronized) if prolonged QT or CHF Adenosine IV Dose: Amiodarone IV Dose: First dose: mg rapid IV push; follow with First dose: 150 mg over 10 minutes NS flush Repeat as needed if VT recurs Second dose: 12 mg if required Follow by maintenance infusion of mg/min for first hours Sotalol IV Dose: 100 mg (1.5 mg/kg) over minutes Avoid if prolonged QT Figure D3 ACLS algorithm for treatment of tachycardia with pulse ABCs, airway, breathing, and circulation; BPM, beats per minute; CHF, congestive heart failure; CPR, cardiopulmonary resuscitation; ECG, electrocardiogram; IV, intravenous; J, joules; NS, normal (0.9%) saline; QRS, QRS interval on ECG; QT, QT interval on ECG; VT, ventricular tachycardia A P P E N D I X E Tables of Height, Predicted Body Weight (PBW), and Tidal Volumes of 4-to-8 mL/kg PBW for Females and Males Acute Respiratory Distress Syndrome Clinical Trials Network (ARDS Network or ARDSNet), National Institutes of Health (NIH), National Heart, Lung and Blood Institute (NHLBI) TABLE E1 n Predicted Body Weight (PBW) and Tidal Volume/kg PBW for Females* Height feet, inches (total in inches) PBW (kg) mL mL mL mL mL 4´ 0˝ (48) 4´ 1˝ (49) 4´ 2˝ (50) 4´ 3˝ (51) 4´ 4˝ (52) 4´ 5˝ (53) 4´ 6˝ (54) 4´ 7˝ (55) 4´ 8˝ (56) 4´ 9˝ (57) 4´ 10˝ (58) 4´ 11˝ (59) 5´ 0˝ (60) 5´ 1˝ (61) 5´ 2˝ (62) 5´ 3˝ (63) 5´ 4˝ (64) 5´ 5˝ (65) 5´ 6˝ (66) 5´ 7˝ (67) 5´ 8˝ (68) 5´ 9˝ (69) 5´ 10˝ (70) 5´ 11˝ (71) 6´ 0˝ (72) 6´ 1˝ (73) 6´ 2˝ (74) 17.9 20.2 22.5 24.8 27.1 29.4 31.7 34 36.3 38.6 40.9 43.2 45.5 47.8 50.1 52.4 54.7 57 59.3 61.6 63.9 66.2 68.5 70.8 73.1 75.4 77.7 72 81 90 99 108 118 127 136 145 154 164 173 182 191 200 210 219 228 237 246 256 265 274 283 292 302 311 90 101 113 124 136 147 159 170 182 193 205 216 228 239 251 262 274 285 297 308 320 331 343 354 366 377 389 107 121 135 149 163 176 190 204 218 232 245 259 273 287 301 314 328 342 356 370 383 397 411 425 439 452 466 125 141 158 174 190 206 222 238 254 270 286 302 319 335 351 367 383 399 415 431 447 463 480 496 512 528 544 143 162 180 198 217 235 254 272 290 309 327 346 364 382 401 419 438 456 474 493 511 530 548 566 585 603 622 994 995 APPENDIX E—TABLES OF HEIGHT FOR MALES AND FEMALES TABLE E1 n Predicted Body Weight (PBW) and Tidal Volume/kg PBW for Females*—Continued Height feet, inches (total in inches) PBW (kg) mL mL mL mL mL 6´ 3˝ (75) 6´ 4˝ (76) 6´ 5˝ (77) 6´ 6˝ (78) 6´ 7˝ (79) 6´ 8˝ (80) 6´ 9˝ (81) 6´ 10˝ (82) 6´ 11˝ (83) 7´ 0˝ (84) 80 82.3 84.6 86.9 89.2 91.5 93.8 96.1 98.4 100.7 320 329 338 348 357 366 375 384 394 403 400 412 423 435 446 458 469 481 492 504 480 494 508 521 535 549 563 577 590 604 560 576 592 608 624 641 657 673 689 705 640 658 677 695 714 732 750 769 787 806 TABLE E2 n Predicted Body Weight (PBW) and Tidal Volume/kg PBW for Males* Height feet, inches (total in inches) 4´ 0˝ (48) 4´ 1˝ (49) 4´ 2˝ (50) 4´ 3˝ (51) 4´ 4˝ (52) 4´ 5˝ (53) 4´ 6˝ (54) 4´ 7˝ (55) 4´ 8˝ (56) 4´ 9˝ (57) 4´ 10˝ (58) 4´ 11˝ (59) 5´ 0˝ (60) 5´ 1˝ (61) 5´ 2˝ (62) 5´ 3˝ (63) 5´ 4˝ (64) 5´ 5˝ (65) 5´ 6˝ (66) 5´ 7˝ (67) 5´ 8˝ (68) 5´ 9˝ (69) 5´ 10˝ (70) 5´ 11˝ (71) 6´ 0˝ (72) 6´ 1˝ (73) 6´ 2˝ (74) 6´ 3˝ (75) 6´ 4˝ (76) PBW (kg) 22.4 24.7 27 29.3 31.6 33.9 36.2 38.5 40.8 43.1 45.4 47.7 50 52.3 54.6 56.9 59.2 61.5 63.8 66.1 68.4 70.7 73 75.3 77.6 79.9 82.2 84.5 86.8 mL mL mL mL mL 90 99 108 117 126 136 145 154 163 172 182 191 200 209 218 228 237 246 255 264 274 283 292 301 310 320 329 338 347 112 124 135 147 158 170 181 193 204 216 227 239 250 262 273 285 296 308 319 331 342 354 365 377 388 400 411 423 434 134 148 162 176 190 203 217 231 245 259 272 286 300 314 328 341 355 369 383 397 410 424 438 452 466 479 493 507 521 157 173 189 205 221 237 253 270 286 302 318 334 350 366 382 398 414 431 447 463 479 495 511 527 543 559 575 592 608 179 198 216 234 253 271 290 308 326 345 363 382 400 418 437 455 474 492 510 529 547 566 584 602 621 639 658 676 694 Continued on following page 996 APPENDIX E—TABLES OF HEIGHT FOR MALES AND FEMALES TABLE E2 n Predicted Body Weight (PBW) and Tidal Volume/kg PBW for Males*—Continued Height feet, inches (total in inches) 6´ 5˝ (77) 6´ 6˝ (78) 6´ 7˝ (79) 6´ 8˝ (80) 6´ 9˝ (81) 6´ 10˝ (82) 6´ 11˝ (83) 7´ 0˝ (84) PBW (kg) mL mL mL mL mL 89.1 91.4 93.7 96 98.3 100.6 102.9 105.2 356 366 375 384 393 402 412 421 446 457 469 480 492 503 515 526 535 548 562 576 590 604 617 631 624 640 656 672 688 704 720 736 713 731 750 768 786 805 823 842 *See Chapter 73, Box 73.3, for details of low tidal volume lung protective ventilatory strategy © ARDS Network ... general, the clinical course of encephalopathy is regarded as the most informative datum in a particular patient the deeper the coma, the worse the outcome The etiology of the ALF is the most... as well as the pathophysiology, clinical features, and therapy of the serotonin syndrome Brent J: Fomepizole for ethylene glycol and methanol poisoning N Engl J Med 360 :22 16 -22 23, 20 09 This case... techniques for the poisoned patient: a review for the intensivist J Intensive Care Med 25 :139-148, 20 10 This is a review of the indications for toxin removal by extracorporeal means, and the advantages