e2 74 Mayer ML, Westbrook GL, Vyklicky L Sites of antagonist action on N methyl d aspartatic acid receptors studied using fluctuation analysis and a rapid perfusion technique J Neurophysiol 1988;60 64[.]
e2 48 Berkenbosch JW, Fichter CR, Tobias JD The correlation of the bispectral index monitor with clinical sedation scores during mechanical ventilation in the pediatric intensive care unit Anesth Analg 2002;94:506-511 49 Grindstaff R, Tobias JD Applications of bispectral index monitoring in the pediatric intensive care unit J Intensive Care Med 2004;19:111-116 50 Wildsmith JA, Brown DT, Paul D, et al Structure-activity relationships in differential nerve block at high and low frequency stimulation Br J Anaesth 1989;63:444-452 51 Covino BG Pharmacology of local anaesthetic agents Br J Anaesth 1986; 58:701-716 52 Wildsmith JA, Gissen AJ, Takman B, et al Differential nerve blockade: esters vs amides and the influence of pKa Br J Anaesth 1987;59:379-384 53 Butterworth JF, Strichartz GR Molecular mechanisms of local anesthesia: a review Anesthesiology 1990;72:711-734 54 Johns RA, DiFazio CA, Longnecker DE Lidocaine constricts or dilates rat arterioles in a dose-dependent manner Anesthesiology 1985;62:141-144 55 Scott DB, McClure JH, Giasi RM, et al Effects of concentration of local anesthetic drugs in extradural block Br J Anaesth 1980; 52:1033-1037 56 Oberndorfer U, Marhofer P, Bosenberg A, et al Ultrasonographic guidance for sciatic and femoral nerve blocks in children Br J Anaesth 2007;98:797-801 57 Schwemmer U, Markus CK, Greim CA, et al Sonographic imaging of the sciatic nerve and its division the popliteal fossa in children Paediatr Anaesth 2004;14:1005-1008 58 Bernards CM, Hadzic A, Suresh S, Neal JM Regional anesthesia in anesthetized or heavily sedated patients Reg Anesth Pain Med 2008; 33:449-460 59 Marhofer P, Sitzwohl C, Greher M, et al Ultrasound guidance for infraclavicular brachial plexus anaesthesia in children Anaesthesia 2004;59:642-646 60 Bhalla T, Sawardekar A, Dewhirst E, et al Ultrasound guided trunk and core blocks in infants and children J Anesth 2013;27:109-123 61 Scott DB, McClure JH, Giasi RM, et al Effects of concentration of local anesthetic drugs in extradural block Br J Anaesth 1980;52: 1033-1037 62 Braid DP, Scott DB The systemic absorption of local analgesic drugs Br J Anaesth 1965;37:394-404 63 Swerdlow M, Jones R The duration of action of bupivacaine, prilocaine, and lignocaine Br J Anaesth 1970;42:335-339 64 Tucker GT, Mather LE Clinical pharmacokinetics of local anesthetics Clin Pharmacokinet 1979;4:241-278 65 Moller RA, Covino BG Cardiac electrophysiologic effects of lidocaine and bupivacaine Anesth Analg 1988;67:107-114 66 Eng HC, Ghosh SM, Chin KJ Practical use of local anesthetics in regional anesthesia Curr Opin Anaesthesiol 2014;27:382-387 67 Neal JM, Mulroy MF, Weinberg GL American Society of Regional Anesthesia and Pain Medicine American Society of Regional Anesthesia and Pain Medicine checklist for managing local anesthetic systemic toxicity: 2012 version Reg Anesth Pain Med 2012;37:16-18 68 Neil JM, Barrington MJ, Fettiplace MR, et al, The 3rd American Society of Regional Anesthesia and Pain Medicine practice advisory on local anesthetic systemic toxicity Reg Anesth Pain Med 2018;43:113-123 69 Concas A, Santoro G, Mascia MP, et al The general anesthetic propofol enhances the function of alpha aminobutyric acid-coupled chloride channel in the rate cerebral cortex J Neurochem 1990;55:2135-2138 70 Ho IK, Harris RA Mechanism of action of barbiturates Annu Rev Pharmacol Toxicol 1981;21:83-111 71 Johnston GA, Willow M GABA and barbiturate receptors Trends Pharmacol Sci 1982;3:328-330 72 Olsen RW Drug interactions at the GABA receptor-ionophore complex Annu Rev Pharmacol Toxicol 1982;22:245-277 73 MacDonald JF, Miljkovic Z, Pennefather P Use-dependent block of excitatory amino acid currents in cultured neurons by ketamine J Neurophysiol 1987;58:251-266 74 Mayer ML, Westbrook GL, Vyklicky L Sites of antagonist action on N-methyl-d-aspartatic acid receptors studied using fluctuation analysis and a rapid perfusion technique J Neurophysiol 1988;60:645-663 75 Vincent JP, Cavey D, Kamenka JM, et al Interaction of phencyclinidines with the muscarinic and opiate receptors in the central nervous system Brain Res 1978;152:176-182 76 Michenfelder JD, Theye RA Cerebral protection by thiopental during hypoxia Anesthesiology 1973;39:510-517 77 Michenfelder JD, Milde JH, Sundt Jr TM Cerebral protection by barbiturate anesthesia Arch Neurol 1976;33:345-350 78 Langsjo JW, Maksimow A, Salmi E, et al S-ketamine anesthesia increases cerebral blood flow in excess of the metabolic needs in humans Anesthesiology 2005;103:258-268 79 Bourgoin A, Albanese J, Wereszcczynski N, et al Safety of sedation with ketamine in severe head injury patients: comparison with sufentanil Crit Care Med 2003;31:711-717 80 Mayberg TS, Lam AM, Matta BF Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/ nitrous oxide anesthesia in patients undergoing craniotomy Anesth Analg 1995;81:84-89 81 Scherzer D, Leder M, Tobias JD Pro-con debate: etomidate or ketamine for rapid sequence intubation in pediatric patients? J Pediatr Pharmacol Ther 2012;17:142-149 82 Modica PA, Tempelhoff R, White PF Pro and anticonvulsant effects of anesthetics Part I Anesth Analg 1990;70:303-315 83 Modica PA, Tempelhoff R, White PF Pro and anticonvulsant effects of anesthetics Part II Anesth Analg 1990;70:433-444 84 Carson IW, Moore J, Balmer JR, et al Laryngeal competence with ketamine and other drugs Anesthesiology 1973;38:128-133 85 Bourke DL, Malit LA, Smith TC Respiratory interactions of ketamine and morphine Anesthesiology 1987;66:153-156 86 Hirshman CA, Downes H, Farbood A, Bergman NA Ketamine block of bronchospasm in experimental canine asthma Br J Anaesth 1979;51:713-718 87 Eames WO, Rooke GA, Sai-Chuen R, Bishop M Comparison of the effects of etomidate, propofol, and thiopental on respiratory resistance after tracheal intubation Anesthesiology 1996;84:1307-1311 88 Pizov R, Brown RH, Weiss YS, et al Wheezing during induction of general anesthesia in patients with and without asthma A randomized, blinded trial Anesthesiology 1995;82:1111-1116 89 Chih-Chung L, Ming-Hwang S, Tan PPC, et al Mechanisms underlying the inhibitory effect of propofol on the contraction of canine airway smooth muscle Anesthesiology 1999;91:750-759 90 Pedersen CM, Thirstrup S, Nielsen-Kudsk JE Smooth muscle relaxant effects of propofol and ketamine in isolated guinea-pig tracheas Eur J Pharmacol 1993;238:75-80 91 Chamberlain JH, Sede RG, Chung DC Effect of thiopentone on myocardial function Br J Anaesth 1977;49:865-870 92 Claeys MA, Gepts E, Camu F Hemodynamic changes during anaesthesia induced and maintained with propofol Br J Anaesth 1988; 60:3-9 93 Cullen PM, Turtle M, Prys-Roberts C, et al Effects of propofol anesthesia on baroreflex activity in humans Anesth Analg 1987;66: 1115-1120 94 Tritapepe L, Voci P, Marino P, et al Calcium chloride minimizes the hemodynamic effects of propofol in patients undergoing coronary artery bypass grafting J Cardiothorac Vasc Anesth 1999;13:150-153 95 Sochala C, Van Deenen D, De Ville A, Govaerts MJM Heart block following propofol in a child Paediatr Anaesth 1999;9:349-351 96 Egan TD, Brock-Utne JG Asystole and anesthesia induction with a fentanyl, propofol, and succinylcholine sequence Anesth Analg 1991;73:818-820 97 Gooding JM, Weng JT, Smith RA, et al Cardiovascular and pulmonary response following etomidate induction of anesthesia in patients with demonstrated cardiac disease Anesth Analg 1979;58:40-41 98 Tarnow J, Hess W, Kline W Etomidate, althesin and thiopentone as induction agents for coronary artery surgery Can Anaesth Soc J 1980;27:338-344 e3 99 Wagner RL, White PF Etomidate inhibits adrenocortical function in surgical patients Anesthesiology 1984;61:647-651 100 Wagner RL, White PF, Kan PB, et al Inhibition of adrenal steroidogenesis by the anesthetic etomidate N Engl J Med 1984;310:1415-1421 101 Sprung CL, Annane D, Keh D, et al CORTICUS study group: hydrocortisone therapy for patients with septic shock JAMA 2002;288:862-871 102 White PF, Way WL, Trevor AJ Ketamine—its pharmacology and therapeutic uses Anesthesiology 1982;56:119-136 103 Dewhirst E, Frazier WJ, Leder M, et al Cardiac arrest following ketamine administration for rapid sequence intubation J Intensive Care Med 2013;28:375-379 104 Smith I, White PF, Nathanson M, et al Propofol: an update on its clinical use Anesthesiology 1994;81:1005-1043 105 Crawford M, Pollock J, Anderson K, et al Comparison of midazolam with propofol for sedation in outpatient bronchoscopy Br J Anaesth 1993;70:419-422 106 Fine PG, Hare BD The pathways and mechanisms of pain and analgesia: a review and clinical perspective Hosp Formul 1985;20:972-985 107 Bailey PL, Wilbrink J, Zwanikken P, et al Anesthetic induction with fentanyl Anesth Analg 1985;64:48-53 108 Shafer SL, Varvel JR Pharmacokinetics, pharmacodynamics and rational opioid selection Anesthesiology 1991;74:53-63 109 Mather LE Pharmacokinetic and pharmacodynamic profiles of opioid analgesics: a sameness amongst equals? Pain 1990;43:3-6 110 DiGiusto M, Bhalla T, Martin D, et al Patient-controlled analgesia in the pediatric population: morphine versus hydromorphone J Pain Res 2014;7:471-475 111 Burkle H, Dunbar S, Van Aken H Remifentanil: a novel, shortacting, mu opioid Anesth Analg 1996;83:646-651 112 Ross AK, Davis PJ, Dear GL, et al Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures Anesth Analg 2001;93:1393-1401 113 Davis PJ, Galinkin J, McGowan FX, et al A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy I Emergence and recovery profiles Anesth Analg 2001;93:1380-1386 114 Galinkin JL, Davis PJ, McGowan FX, et al A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy II Perioperative breathing patterns in neonates and infants with pyloric stenosis Anesth Analg 2001;93:1387-1392 115 Keats AS The effects of drugs on respiration in man Annu Rev Pharmacol Toxicol 1985;25:41-65 116 Urthaler F, Isobe JH, James T Direct and vagally mediated chronotropic effects of morphine studied by selective perfusion of the sinus node of awake dogs Chest 1975;68:222-228 117 Zelis R, Mansour EJ, Capone RJ, et al The cardiovascular effects of morphine The peripheral capacitance and resistance vessels in human subjects J Clin Invest 1974;54:1247-1258 118 Tobias JD Applications of nitrous oxide for procedural sedation in the pediatric population Pediatr Emerg Care 2013;29:245-265 119 Smith NT, Eger EJ II, Stoelting RK, et al The cardiovascular and sympathomimetic responses to the addition of nitrous oxide to halothane in man Anesthesiology 1970;32:410-421 120 Fink BR Diffusion anoxia Anesthesiology 1955;16:511-519 121 Deacon R, Lumb M, Perry J, et al Selective inactivation of vitamin B12 in rats by nitrous oxide Lancet 1978;2:1023-1024 122 Hadzic A, Glab K, Sanborn KV, et al Severe neurologic deficit after nitrous oxide anesthesia Anesthesiology 1995;83:863-866 123 Eger EI II, Saidman LJ Hazards of nitrous oxide anesthesia in bowel obstruction and pneumothorax Anesthesiology 1965;26:61-66 124 Myles PS, Leslie K, Chan MT, et al The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial Lancet 2014;384:1446-1454 125 Ko H, Kaye AD, Urman RD Nitrous oxide and perioperative outcomes J Anesth 2014;28:420-428 126 Eckenhoff R Do specific or nonspecific interactions with proteins underlie inhalational anesthetic action? Mol Pharmacol 1998;54: 610-615 127 Morray JP, Geiduschek JM, Ramamoorthy C, et al Anesthesia-related cardiac arrest in children: initial findings of the Pediatric Perioperative Cardiac Arrest (POCA) Registry Anesthesiology 2000;93:6-14 128 Tobias JD Inhalational anesthesia: basic pharmacology, end organ effects, and applications in status asthmaticus J Intensive Care Med 2009;24:361-371 129 Subcommittee on the National Halothane Study of the Committee on Anesthesia Possible association between halothane anesthesia and postoperative hepatic necrosis JAMA 1966;197:775-788 130 Kenna JG, Jones RM The organ toxicity of inhaled anesthetics Anesth Analg 1995;81(suppl):S51-S66 131 Brown Jr BR, Gandolfi AJ Adverse effects of volatile anesthetics Br J Anaesth 1987;59:14-23 132 Pohl LR, Satoh H, Christ DD, et al The immunologic and metabolic basis of drug hypersensitivities Annu Rev Pharmacol 1988; 28:367-387 133 Wark HJ Postoperative jaundice in children—the influence of halothane Anaesthesia 1983;38:237-242 134 Warner LO, Beach TP, Garvin JP, et al Halothane and children: the first quarter century Anesth Analg 1984;63:838-840 135 Mazze RI, Calverley RK, Smith NT Inorganic fluoride nephrotoxicity: prolonged enflurane and halothane anesthesia in volunteers Anesthesiology 1977;46:265-271 136 Morio M, Fujii K, Satoh N, et al Reaction of sevoflurane and its degradation products with soda lime Toxicity of the byproducts Anesthesiology 1992;77:1155-1164 137 Frink Jr EJ, Malan TP, Morgan SE, et al Quantification of the degradation products of sevoflurane in two CO2 absorbents during low-flow anesthesia in surgical patients Anesthesiology 1992;77:1064-1069 138 Mazze RI The safety of sevoflurane in humans Anesthesiology 1992;77:1062-1063 139 Kopman AF, Ng J, Zank LM, et al Residual postoperative paralysis: pancuronium versus mivacurium; does it matter? Anesthesiology 1996;85:1253-1259 140 Kopman AF, Yee PS, Neuman GC Correlation of the train-of-four fade ratio with clinical signs and symptoms of residual curarization in awake volunteers Anesthesiology 1997;86:765-771 141 Tobias JD Current evidence for the use of sugammadex in children Paediatr Anaesth 2017;27:118-125 142 Ghijselings I, Rex S Hydroxyethyl starches in the perioperative period A review on the efficacy and safety of starch solutions Acta Anaesthesiol Belg 2014;65:9-22 143 Foster BA, Tom D, Hill V Hypotonic versus isotonic fluids in hospitalized children: a systematic review and meta-analysis J Pediatr 2014;165:163-169 144 Austin KL, Stapleton JV, Mather LE Multiple intramuscular injections: a major source of variability in analgesic response to meperidine Pain 1980;8:47-62 145 American Society of Anesthesiologists Practice guidelines for acute pain management in the perioperative setting Anesthesiology 1995;82:1071-1081 146 Austin KL, Stapleton JV, Mather LE Relationship between blood meperidine concentrations and analgesic response: a preliminary report Anesthesiology 1980;53:460-466 147 Dahlstrom B, Tamsen A, Paalzow L, et al Patient-controlled analgesic therapy Part IV Pharmacokinetics and analgesic plasma concentration of morphine Clin Pharmacokinet 1982;7:266-279 148 Tamsen A, Hartvig P, Fagerlund C, et al Patient-controlled analgesic therapy Part II Individual analgesic demand and analgesic plasma concentrations of pethidine in postoperative pain Clin Pharmacokinet 1982;7:164-175 149 Tobias JD Weak analgesics and nonsteroidal anti-inflammatory agents in the management of children with acute pain Pediatr Clin North Am 2000;47:527-543 e4 Abstract: General anesthesia includes a combination of medications to provide amnesia, analgesia, muscle relaxation, and attenuation of the sympathetic nervous system’s response to surgical trauma The phases of general anesthesia include induction, maintenance, and emergence This chapter reviews the sequence of events involved in perioperative care, including the preoperative evaluation, intraoperative monitoring, the pharmacology of intraoperative anesthetic agents, and the development of the postoperative analgesia plan Key words: General anesthesia, preoperative evaluation, intraoperative monitoring, local anesthetic agents, volatile anesthetic agents, intravenous anesthetic agents, opioids 130 Malignant Hyperthermia CHRISTOPHER M EDWARDS AND BARBARA W BRANDOM • Risk factors for malignant hyperthermia (MH) include a family history of severe hyperthermia or sudden hypermetabolic state during anesthesia with exposure to succinylcholine and/or potent inhalation anesthetics, and ryanodine receptor type one myopathy Clinical presentation includes uncontrollable hypercarbia and rapidly increasing temperature due to excessive metabolism Tachycardia, muscle rigidity, acidemia, and rhabdomyolysis are frequent The clinical diagnosis of malignant hyperthermia may be confirmed by genetic testing or muscle contracture testing Malignant hyperthermia (MH) was first described in the 1960s, and the case fatality remained greater than 70% through the 1970s Since then, advances in intraoperative monitoring, decreased use of succinylcholine in pediatric anesthesiology, and the discovery of dantrolene as an effective treatment have reduced morbidity and mortality substantially.1 However, the apparent genetic susceptibility to MH is 1:2000,2 and deaths continue to occur when MH is not suspected and treated soon enough in the operating room Further, many of these deaths occur in otherwise healthy patients presenting for low- or intermediate-risk surgeries.3 There remains a great opportunity for saving lives with improved understanding, timely diagnosis, and effective treatment of MH The physician in the pediatric intensive care unit (PICU) may first encounter a patient with MH in transfer from the operating room or from an outpatient facility where general anesthesia was given and treatment for acute MH was begun Alternatively, the intensivist may be the first to entertain the diagnosis of MH in a patient admitted to the ICU for medical care or postoperative management In either case, the ability to deliver timely and comprehensive care is critical to the patient surviving this potentially fatal syndrome Pathophysiology MH is a hypermetabolic reaction of genetically abnormal skeletal muscle, typically triggered in humans by the exposure to volatile anesthetics and/or the depolarizing muscle relaxant succinylcholine If not promptly recognized and aggressively treated, clinical effects of fulminant MH may rapidly progress from muscle injury to multiorgan system failure and death The underlying defect is 1560 • • PEARLS Treatment consists of administration of repeated doses of 2.5 mg/kg of dantrolene intravenously until metabolism and muscle tone are normal The patient should be cooled aggressively if temperature is higher than 39°C Treat hyperkalemia, myoglobinuria, disseminated intravascular coagulation, and cerebral edema as needed After initial treatment, mg/kg of dantrolene should be given every to hours for at least 24 hours, because 20% of patients experience an exacerbation or recrudescence of MH a sudden, sustained increase in the concentration of calcium ion in the sarcoplasm.4 Resultant increased skeletal muscle metabolism increases carbon dioxide (CO2) production severalfold Even with markedly increased minute ventilation, it may be difficult to achieve normocarbia The associated lactic acid production overwhelms the body’s buffering capacity Increased oxygen (O2) demand and the concomitant sympathetic response stress the cardiovascular system MH can progress rapidly to severe mixed acidosis, hyperkalemia, elevated temperature as in heatstroke,5 and rhabdomyolysis Renal failure, disseminated intravascular coagulation (DIC), cerebral edema, pulmonary edema, dysrhythmias, and cardiovascular collapse are potential consequences of fulminant MH Before dantrolene, the mortality rate of MH was 70% Symptomatic therapy—including mechanical ventilation, active cooling, administration of bicarbonate, expansion of intravascular volume, and treatment of dysrhythmias—can prolong life during an episode of fulminant MH However, by far, the most rapid and effective therapy is intravenous dantrolene.6 In the majority of MH-susceptible (MHS) mammals, skeletal muscle calcium dysregulation results from a defect in the ryanodine receptor type one channel (RYR1)7 calcium release channel, producing increased sensitivity to agonists8,9 and decreased sensitivity to inhibitors Furthermore, excitation-coupled calcium entry (ECCE) is greater than normal in myotubes expressing MHS RYR1.10 Dantrolene increases the affinity of the ryanodine receptor for the endogenous inhibitor magnesium11 and inhibits ECCE in both MHS and normal muscle Store-operated calcium entry (SOCE) is another process, occurring after depletion of SR calcium, that moves extracellular calcium into the myoplasm SOCE is coupled to RYR1 and decreased by dantrolene.12 CHAPTER 130 Malignant Hyperthermia Genetics MH susceptibility is a syndrome with autosomal-dominant inheritance, incomplete penetrance, and variable expressivity The first-degree relatives of an MHS individual are treated as MHS until they have normal results of a caffeine-halothane contracture test (CHCT) Incomplete penetrance means that a person with a mutation recognized to be causative of MH may not experience MH during the first or subsequent exposures to MH trigger agents Multifactorial inheritance may be relevant.2,13 Variable expressivity means that clinical symptoms of MH vary from minor to fulminant depending on factors such as anesthetic agent, genetics, and temperature.14–16 Severe MH episodes are more often observed in males and in muscular individuals.17–19 The primary genetic locus of MH (MHS 1) is the ryanodine receptor gene (RYR1) on chromosome 19q13.1 Variants associated with MH susceptibility are found throughout RYR1 and are thought to account for 50% to 70% of families affected by MH.20 Two other genes, CACNA1S on chromosome 1q32 and STAC3 on chromosome 12, are now recognized to contain MH mutations CACNA1S encodes the main subunit of the dihydropyridine receptor that interacts with the RYR1 channel and accounts for approximately 1% of MHS families.21 The STAC3 protein, involved in excitation-contraction coupling, was first found to be abnormal in a group of myopathic Lumbee Indian families with MH susceptibility.22 In families with a known MH-causative genetic mutation, genetic analysis is a useful initial step in the diagnosis of MH susceptibility.23,24 The roles of deoxyribonucleic acid (DNA)based tests and muscle contracture tests are discussed later While the genetic risk of developing MH was historically considered an “all-or-none” phenomenon, there is emerging evidence that some RYR1 variants have more profound functional consequences.25 This may account for some of the variability in clinical presentation of MH For example, one RYR1 mutation has been shown to affect vascular smooth muscle, leading to a prolonged bleeding phenotype.26 Clinical Recognition of Malignant Hyperthermia The clinical presentation and initial signs of an MH episode are varied and nonspecific (Box 130.1).27 However, anesthesiologists and critical care physicians must promptly diagnose and treat MH, as the likelihood of complications increases 2.9 times for every 2°C increase in maximum core temperature and 1.6 times for every 30 minutes of time between the appearance of the first clinical sign of MH and the beginning of dantrolene administration.17 In a study of 129 MH reactions in Canadians, the most frequent clinical signs of MH were hyperthermia greater than 38.8°C (in 67%), sinus tachycardia (62%), and hypercarbia (52%) Other MH signs noted in this group include masseter rigidity, total body rigidity, arrhythmia, skin mottling, and cyanosis.28 This report is consistent with data from the North American MH Registry.17,29 A patient’s muscles may be rigid enough to pull the legs above the horizontal Laboratory findings frequently include mixed respiratory and metabolic acidosis, hyperkalemia, myoglobinuria, and increased serum creatine kinase (CK) However, rhabdomyolysis does not occur during every MH episode.30 1561 • BOX 130.1 Positive Findings Consistent With Malignant Hyperthermia • History of recent exposure to trigger agent, including volatile anesthetic agents or succinylcholine • Family or personal history of MH susceptibility • Total body rigidity • Masseter spasm • Inappropriately elevated (38.8°C) or rapidly increasing temperature (.1.5°C over min) • Inappropriate tachypnea • Profuse sweating • Mottled, cyanotic skin • Dark urine, urine dipstick testing shows a positive result from blood without red cells in the sediment and no hemolysis • Unexplained, excessive bleeding • Unexplained ventricular tachycardia or fibrillation • Inappropriate hypercarbia (venous Paco2 65 mm Hg, arterial Paco2 55 mm Hg) if the patient is receiving positive-pressure ventilation or is spontaneously breathing with greater than normal minute ventilation • Arterial base excess more negative than 28 mEq/L • Arterial pH ,7.25 • Potassium concentration mEq/L • Creatine kinase 10,000 IU/L MH, Malignant hyperthermia; Paco2, partial pressure of arterial carbon dioxide • BOX 130.2 Differential Diagnosis of Malignant Hyperthermia in the Intensive Care Unit Neuroleptic malignant syndrome Exertional hyperthermia and heat stroke Serotonin syndrome Sepsis associated with renal and respiratory failure Central nervous system injury Postoperative fever Thyrotoxicosis Rhabdomyolysis Pheochromocytoma Porphyria Allergic reaction secondary to medications Blood transfusion reactions Administration of hypertonic dye, such as diatrizoate intrathecally Drug abuse (cocaine, amphetamines, Ecstasy) Drug withdrawal Iatrogenic overheating Delirium tremens Differential Diagnosis Given the nonspecific nature of many of the common signs of MH, a number of other medical, metabolic, and endocrinologic pathologies should be considered in the differential diagnosis These include sepsis, drug abuse and withdrawal, thyroid storm,31 and untreated pheochromocytoma (Box 130.2).32 In the intensive care unit (ICU), a septic patient with kidney disease or chronic lung disease may exhibit fever, tachycardia, mixed respiratory and metabolic acidosis, and hyperkalemia If sepsis, cardiovascular failure, central nervous system injury, heat stroke, or other medical or surgical conditions could have produced the abnormal vital signs, then these more common diagnoses must be pursued and ... and hypercarbia (52%) Other MH signs noted in this group include masseter rigidity, total body rigidity, arrhythmia, skin mottling, and cyanosis.28 This report is consistent with data from the... analgesic therapy Part II Individual analgesic demand and analgesic plasma concentrations of pethidine in postoperative pain Clin Pharmacokinet 1982;7:164-175 149 Tobias JD Weak analgesics and... surgical trauma The phases of general anesthesia include induction, maintenance, and emergence This chapter reviews the sequence of events involved in perioperative care, including the preoperative