Hypermetabolism during bilateral single-lung transplantation requiring cardiopulmonary bypass

Hypermetabolism During Bilateral Single-Lung Transplantation Requiring Cardiopulmonary Bypass Mark A. Chaney, MD

IGNIFICANT hypermetabollsm is fortunately only rarely encountered during the perioperative period. Persistent hypermetabolism despite hypothermic cardiopulmonary bypass, implied by low mixed venous oxygen saturation, offers a formidable challenge to the anesthesiologist. Described in this report is an episode of significant hypermetabolism that occurred during bilateral single-lung transplantation and required the assist of cardiopulmonary bypass.

S

CASE REPORT

The patient was a 21-year-old 52-kg man with cystic fibrosis transferred to this institution for bilateral singlelung transplantation. He had been hospitalized over the prior 2 weeks for medical treatment of fever, cough, and excesswe sputum production. Past medical history was significant for cystic fibrosis diagnosed at age 2. Past surgical history included "eye surgery" as a young child, appendectomy at age 8, right upper lobectomy at age 19, and sinus surgeries at ages 19 and 20. All prior surgeries were performed at another institution and were reportedly unremarkable. No famihal history of anesthetic or surgical problems could be elicited. Medications on transfer included albuterol, prednisone, trimethopnm, sulfamethoxazole, omeprazole, pancrelipase, and multivitamins. At time of transfer, the patient was afebrile, yet the white blood cell count was 58,700/mm 3. On arrival at this institution, the patient was noted to be in severe respiratory distress. A decision was then made to initiate mechanical ventilatory support before transfer to the operating room. At 0545, the trachea was easily intubated with a single-lumen endotracheal tube after intravenous administration of etomidate (10 mg) and succinylcholine (100 rag). No muscular rigidity was documented during intubation, and the patient remained hemodynamically stable. The first arterial blood gas sample, at 0621, showed significant hypercarbia and acidosis despite a minute ventilation of 8 L/ram (Table 1). Minute ventilation was then doubled to 16 L/min by doubhng the respiratory rate. The next arterial blood gas sample, at 0826, showed that this maneuver had no effect on the hypercarbia and acidosis. A chest radiograph showed that the endotracheal tube was in proper position and showed extensive peribronchial inflammatory disease evenly distributed throughout both lungs that was consistent with cystic fibrosis. A bronchoscopy was performed that showed gross amounts of purulent secretions. A wad of gum was also extracted from the right mainstem bronchus. The patient was transferred to the operating room at 1028. Blood pressure was 80/40 mmHg and heart rate was 130 bpm (sinus rhythm). Intravenous norepmephrlne (6 p~g/min) was required to maintain an adequate blood pressure. An arterial blood gas sample on arrival showed only a mild improvement in hypercarbia and acidosis despite a minute ventilation of 16 L/rain. Esophageal temperature at this time was 36.0°C. The original plan of the surgeons had been to perform

the bilateral single-lung transplantation without the assist of cardlopulmonary bypass (CPB). Therefore, after intravenous administration of fentanyl (1000 ~g), midazolam (4 mg), and vecuronium (10 rag), the single-lumen endotracheal tube was removed, and a left-sided double-lumen endotracheal tube was inserted. However, it soon became apparent that the hypercarbia and acidosis were resistant to multiple mechanical ventilatory maneuvers, including increasing the minute ventilation to over 20 L/rain. Peak inspiratory airway pressure at this time was 50 em HzO with a tidal volume of 700 mL. Increasing amounts of intravenous norepanephrine were required to maintain an adequate blood pressure and sinus tachycardia persisted. After discussion with the surgeons, it was decided that the patient would not tolerate one-lung ventilation, and the assist of CPB would be required. CPB was initiated at 1205 via an aortic and two-stage atrial cannula. A flow of 2.4 L/min/m 2 was maintained, and cooling was begun to 34.0°C. The highest esophageal temperature before onset of CPB was 36.0°C. Soon after initiation of CPB, it was discovered that the venous oxygen saturation was low. Mechanical problems with the CPB machine and circuit were quickly ruled out, and venous oxygen saturation remained low despite increasing flow to well over 3.0 L / m l n / m z. The hematocrit was 21%. At this time, the possibility that the clinical scenario represented a manifestation of malignant hyperthermia was discussed with the anesthesiologist in charge of the case. A decision was made not to administer dantrolene. Throughout CPB, venous oxygen saturation remained low despite higher than normal flow and adequate hematocrit. Core temperature was held at 34.0°C. Perfusion pressure was maintained between 40 and 70 mmHg without the assistance of vasoconstrictors or vasodilators. Heart rate remained elevated at 110 bpm (sinus rhythm). Urine output was adequate, and no hematuria was noted. Total CPB time was 5 hours 5 minutes. Right-lung ischemia time was 6 hours 15 minutes, and left-lung ischemla time was 7 hours 45 minutes. Separation from CPB occurred at 1710, requiring only moderate amounts of intravenous norepinephrme (6 Ixg/ rain). Blood pressure and heart rate were 110/60 mmHg and 140 bpm (sinus rhythm), respectively. Esophageal temperature was 37.7°C. Immediately after CPB, oxygenation and ventilation were difficult to maintain despite multiple mechanical

From the Department of Anesthestology, Loyola UmversayMedtcal Center, Foster G McGaw Hospaal, Maywood, IL. Address repnnt requests to Mark A Chancy, MD, Assistant Professor of Anesthestology, Department of Anesthesiology, Loyola Umverslty Medwal Center, Foster G. McGaw Hospaal, 2160 S Ftrst Ave, Maywood, IL 60153 Copyright © 1995 by W B. Saunders Company 1053-0770/95/0905-001753 00/0 Key words: hypermetabohsm, sepszs, mahgnant hyperthermta

JournalofCardtothoractc and VascularAnesthesta, Vol 9, No 5 (October), 1995: pp 565-570

565

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MARK A CHANEY

Table 1. Arterial Blood Gas Samples on the Day of Surgery Time

pH

PCO2

PO2

O2SAT

0621 0826 1028 1117 1153 On CPB 1215 A V 1240 A V 1316 A V 1344 A V 1527 A V 1702 A V Off CPB 1734 1757 1838 1901 1942 ICU 2110 2351

7 13 7 13 7.18 7 10 6.95

125 126 103 120 153

319 308 158 160 121

7 16 7 08

92 121

387 56

100% 73%

7 42 7 33

46 62

340 35

100% 60%

7 38 7 37

46 51

259 29

100% 52%

7 41 7 39

39 44

267 25

100% 45%

7.44 7 42

36 39

287 26

100% 50%

7 45 7.38

32 41

412 28

100% 51%

7 7 7 7 7

36 27 24 21 25

45 50 61 58 48

106 52 67 107 148

7 27 7 31

54 40

271 122

Abbreviations" SAT, saturation; ICU, mtensive care unit NOTE During cardiopulmonary bypass (CPB) blood gas samples tdentified as " A " and "V'" represent artenal and venous samples, respecttvely. PCO2 and PO2 values are tn mmHg

ventilatory maneuvers. A bronchoscopy performed at 1835 showed a fair amount of blood clot and mucous in the airways, which were removed. Blood pressure remained stable after CPB, but sinus tachycardia persisted to rates as high as 160 bpm. After chest closure, the double-lumen

endotracheal tube was removed and a single-lumen endotracheal tube was inserted. A bronchoscopy performed after the endotracheal tube change showed open and clear airways. The highest esophageal temperature after CPB was 37.7°C. Adequate urine output after CPB required intravenous furosemide, and no hematuria was noted. Oxygenation and ventilation gradually improved, and the patient was transferred to the intensive care unit at 2015 Mechanical ventilatory support at this time was as follows: respiratory rate 14, tidal volume 800 mL, FIO 2 1.0, and 10 cm HzO positive end-expiratory pressure. Peak inspiratory airway pressure was 40 cm HzO. Improvement continued into postoperative day 1. The acidosis resolved and improved oxygenation and ventilation allowed less aggressive mechanical ventilatory support. Blood pressure remained stable, but sinus tachycardia persisted to rates as high as 148 bpm. The patient remained afebrile and the chest radiograph was clear. However, postoperative day 1 was significant for the occurrence of hematuria and elevated levels of blood urea nitrogen and serum creatinine (Table 2). The white blood cell count also increased to 87,900/mm 3. On postoperative day 2, hver enzymes were significantly increased. Urine output decreased and blood urea mtrogen and serum creatinme levels continued to increase. The patient remained unconscious. On postoperatwe day 3, liver enzymes began to decrease but worsening renal failure required hemodialysis. Blood levels of myoglobin and creatine phosphokinase were significantly elevated. Oxygenation and ventilation continued to improve, and the chest radiograph remained clear. Sputum cultures grew Pseudomonas aerogmosa and moderate colonies of yeast. On postoperative day 4, the patient regained consciousness. Liver enzymes continued to decrease, but hemodialysls was still required for renal failure. A bronchoscopy was performed that showed moderate tracheobronchitis, thick secretions, and intact anastomoses. The patient continued to improve significantly from postoperative day 5 through postoperative day 8. He was awake, alert, and oriented. Liver and renal function continued to improve, and hemodialysis was no longer necessary. Only minimal mechanical ventdatory support was required, and a trial of extubation was considered. However, blood

Table 2 Chnical Laboratory Values DATE Surgery POD 1 POD 2 POD 3 POD 4 POD 5 POD 6 POD 7 POD 8 POD 9

CPK

5050

MYO

10560 6484 4611 2500 1600 941

BUN

CR

21 47 80 118 116 106 88 107 117 135

05 30 3.7 5.1 50 47 4.3 4.8 4.7 4.5

LDH

TBILI

GGT

AP

219

AST 95

ALT 196

1.1

126

177

14070 2360 1322 899 654

10330 1261 505 256 116

13490 5780 3130 1511 785

4.9 74 74 6.8 43

112 109 112 134 135

172 151 176 266 278

390 408

50 40

324 193

27 25

191 118

321 229

Abbreviattons. POD, postoperattve day, CPK, creatlne phosphokmase (IU/L), MYO, serum myoglobm (ng/mL); BUN, blood urea mtrogen (mg/dL), CR, serum creatinine (mg/dL); LDH, lactic dehydrogenase (IU/L), AST, aepartate ammotransferase (IU/L), ALT, alanine ammotransferase (IU/L); TBILI, total bihrubin (mg/dL); GGT, gamma glutamyl transpepttdase (IU/L); AP, alkahne phosphatase (IU/L) NOTE. The normal range for serum myoglobm in the chmcal laboratory is 0 to 75 ng/mL

HYPERMETABOLISM DURING CARDIOPULMONARY BYPASS

cultures grew Pseudomonas aeroginosa and Candida albtcans. He remained afebrile, and the white blood cell count decreased to 18,900/mm 3. On postoperative day 9, the patient developed severe respiratory distress associated with a copious amount of tenacious tracheobronchial secretions that required full mechanical ventilatory support. Chest radiograph showed increased pulmonary interstitial markings and questionable free air in the peritoneal cavity. He remained afebrile, but the white blood cell count acutely increased to 63,300/mm 3. On postoperative day 10, the patient required sedation and muscle paralysis to maintain adequate oxygenation and ventilation. Hemodialysis was resumed for renal failure. A bronchoscopy was performed that showed extensive sloughing of the tracheobronchial mucosa, a grey-black exudate, and intact anastomoses. On postoperative day 11, the patient died abruptly of circulatory instability. Gross autopsy showed a purulent exudate covering the thoracic and abdominal viscera along with a collection of purulent material In the pelvic cavity. Bilateral pulmonary consolidation and pleural effusions (1.0 L each side) were present along with multiple pulmonary abscesses. Both anastomoses were intact. The right lobe of the liver was nodular. Splenomegaly and ascites (3.0 L) also were documented. Examination of skeletal muscle showed extensive necrosis consistent with rhabdomyolysis. DISCUSSION

The mixed venous oxygen saturation hints at the amount of residual oxygen remaining in the bloodstream after global tissue extraction. Although the relationship has never been scientifically demonstrated, it has been used by clinicians since the early 1970s as a tool to gauge adequacy of tissue oxygenation. I Although the mixed venous oxygen saturation presents a unique view of total body oxygen balance, it shows nothing regarding adequacy of tissue oxygenation of any individual vascular bed. The mixed venous oxygen saturation is determined by five fundamental variables: hemoglobin level, arterial blood oxygen saturation, arterial blood oxygen partml pressure, cardiac output, and total body oxygen consumption. 2 A mixed venous oxygen saturation of 75% (POe = 40 mmHg) is believed to indicate adequate tissue oxygenation, whereas values less than 30% ( P O 2 = 20 mmHg) suggest inadequate tissue oxygenation, for the oxygen partial pressure gradient that exists at this level ~s inadequate to allow uptake by tissues. 3 Clinically, a mixed venous oxygen saturation less than 50% that cannot be increased with therapy is reliably associated with a poor outcome. 4 Arguments have been m a d e for 4 and against 5 the routine monitoring of mixed venous oxygen saturation during cardiac surgery. Although caution is needed when interpreting normal or elevated mixed venous oxygen saturation values, low values can usually be interpreted as being compatible with tissue hypoxia? A low mixed venous oxygen saturation value implies either Insufficient oxygen delivery or increased oxygen consumption that has not been compensated for. Chnically, when confronted with a low mixed venous oxygen satura-

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tion, all five fundamental variables that determine the value must be examined. Four of the five variables influence oxygen delivery: hemoglobin level, arterial blood oxygen saturation, arterial blood oxygen partial pressure, and cardiac output. In this patient on CPB, the hemoglobin level was adequate (hematocrit 21%) as was the arterial blood oxygen saturation (saturation 100%) and arterial blood oxygen partial pressure (PO2 = 259 to 412 mmHg). Under these circumstances, cardiac output is analogous to CPB flow, which was higher than normal (CPB flow maintained well over 3.0 L/min/m2). Therefore, in this patient, oxygen dehvery was more than adequate for that which is normally required during hypothermlc CPB. 6 The fifth variable, oxygen consumption, is thus implicated as the cause of low mixed venous oxygen saturation in this patient. The mixed venous oxygen saturation of a patient on hypothermic CPB is typically elevated above 80%. 3,6 The increase in mixed venous oxygen saturation under these circumstances reflects a decrease in oxygen consumption caused by paralysis, 6 sedation, 7 and hypothermia, s Hypothermia also increases the amount of dissolved oxygen in the blood, thus increasing oxygen delivery. 9 The increase in the amount of dissolved oxygen in the blood caused by hypothermia has at times been life-saving during management of severe acute normovolemic hemodilution. 1°,Ia In this patient, therefore, mixed venous oxygen saturation values of approximately 50% while paralyzed and sedated on hypothermic CPB implied a considerable increase in oxygen consumption. The differential diagnosis of increased oxygen consumption, or hypermetabolism, is extensive. Common causes include pain, agitation, shwering, fever, infection, sepsis, seizures, burns, and trauma. Less common causes include thyrotoxicosis, pheochromocytoma, malignant hyperthermia, and multiple system organ failure. In this patient, the most likely cause of hypermetabolism was sepsis. However, the possibility that this scenario represented a manifestation of malignant hyperthermia cannot be ruled out enUrely. Sepsis is the systemic inflammatory response to infection. Common clinical manifestations of sepsis include, but are not limited to, hyperthermia or hypothermm, tachycardia, tachypnea, and leukocytosis or leukopenia. 12 Respiratory alkalosis is often present in the early stages of sepsis, whereas in the late stages metabolic acidosis is present. I3 Severe sepsis is associated with hypotenslon, hypoperfuslon, and organ dysfunction. A subset of severe sepsis, septic shock, is present when hypotenslon persists despite adequate fluid resuscitation, causing perfusion abnormalities and organ dysfunction. 12 The pathogenesis of septic shock is extremely complex. I4 It begins with a nidus of infection. Microorganisms may then either invade the blood stream, causing positive blood cultures, or proliferate at the infected site. The microorganisms release large amounts of various mediators that not only directly affect the host but also initiate release of secondary mediators by the host. The major cardiovascular effects of the exogenous and endogenous mediators are myocardial depression and peripheral vasodilationA 5 Car-

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dlac output also increases because of peripheral vasodilatlon and ventricular dilation, a5 In patients who cannot sustain the increase in cardiac output, peripheral vasoconstriction occurs and cardmc output decreases, is Treatment of septic shock involves utilization of antibiotics, aggressive volume resuscitation, and the use of inotropes and vasopressors. Unfortunately, despite the development of new antibiotics and increased sophistication of critical care, mortality associated with septic shock has not changed an the last 10 years and remains at 40% to 60%. 12,15 Septic shock is characterized by abnormal oxygen utilization. 13An increase in oxygen consumption may occur that is reflected by a decrease in mixed venous oxygen saturation. 15,I6 However, more commonly assocmted with septic shock as a normal or increased mixed venous oxygen saturation despite adequate oxygen delivery, which implies a decrease in oxygen consumptionY 7-19Administration of endotoxin, an exogenous mediator of septic shock, to normal human volunteers causes an increase in mixed venous oxygen saturation. 14 The cause of the decrease in oxygen consumption associated with septic shock is poorly understood yet may involve metabolic derangements, as impaired tissue oxygen extraction, 17,19or shunting of microcirculatory blood flow. 13,15,I9 In human septic shock, an increased mixed venous oxygen saturation indicates decreased tissue oxygen utilization and may predict a poor outcome. 1 A subsequent decrease in mixed venous oxygen saturation may indicate increased tissue oxygen utilization and may suggest clinical improvement of septic shock. 2 This patient exhibited all of the clinical signs of septic shock, including hyperthermia (before transfer), tachycardia, tachypnea, leukocytosis, persistent hypotension despite adequate fluid resuscxtation, and organ dysfunction. The acidosas reflected resparatory (from cystic fibrosis) and metabolic (from septic shock) components. The nidus of infection was likely the lungs because the aarways of patients with cysUc fibrosis are often colonized with microorgamsms that cannot be eradicated even wath aggressive treatment with antibiotics and chest physical therapy. 2° Furthermore, this patient had been hospitalized for 2 weeks before transfer for symptoms suggestive of a pulmonary infection (fever, cough, excessive sputum production). The use of antibiotics and immunosuppressives in this patient may have also increased the risk of developing sepsis from a pulmonary infection, a4The low mixed venous oxygen saturation on hypothermic CPB is likely attributable to an increase an oxygen consumption that is sometimes associated with sepsis. 15,16 This is somewhat surprising because most patients with sepsis exhibit a decrease in oxygen consumption. 2,17q9Perhaps with initiation of CPB, microcirculatory blood flow increased, thus allowing for increased tissue oxygen utilization. Renal and hepatic failure, which developed in this pauent postoperatively, are common complications of septic shock. 12 Findings on gross autopsy (purulent material in abdominal and pelvic cavities) also support the diagnosis of sepsis. Finally, rhabdomyolysis may occur in some patients who develop sepsis. 13,18 Manifestation of malignant hyperthermia during anesthesia and surgery is relatively rare. 21 Reports of malignant

MARK A CHANEY

hyperthermia during surgery involving organ transplantation 22,23or during surgery requiring C P B 24-26 a r e extremely rare. Although the most likely cause of hypermetabolism in this patient was sepsis, the possibility that this scenario represented a manifestation of malignant hyperthermia cannot be entirely ruled out. Malignant hyperthermia is a genetically heterogenous disorder affecting skeletal muscle. The primary defect has yet to be fully elucidated yet the biochemical basis appears to be disordered calcium homeostasis within skeletal muscle that ultimately leads to hypermetabolism. 27 Diagnosis of malignant hyperthermia is confirmed when the hypermetabolic state creates pathognomonic clinical signs and laboratory abnormalities. 21 Classic clinical signs of malignant hyperthermla exhibited by this patient included increased oxygen consumption, increased carbon dioxide production, acidosis, and tachycardia. Two classic clinical signs, muscular rigidity and hyperthermia, were absent. However, muscular rigidity is not always associated with mahgnant hyperthermia, 2s and development of hyperthermia may have been masked by initiation of hypothermic CPB. 26 Classic laboratory abnormalities exhibited by this patient included postoperative elevation of serum creatine phosphokinase and serum myoglobin levels. Both possibly imply malignant hyperthermia-induced rhabdomyolysis. Postoperative renal failure, hepatic failure, and encephalopathy have all been associated with malignant hyperthermia. 25 Past medical and surgical history may yield clues indicating malignant hyperthermia susceptibility. The patient's "eye surgery" as a young child may have been for ptosis or strabismus, conditions that may be associated with an increased susceptibility to malignant hyperthermia. 21 Difficulties with previous anesthetics, in a patient or patient's close relatives, may also indicate an Increased susceptibility to malignant hyperthermia. That this patient underwent five previous uneventful anesthetics and had a negative family history is not uncommon, however, because approximately 20% of malignant hyperthermia episodes are associated with previous uneventful anesthetics and 25% are associated with a negative family history, el Confirmation of malignant hyperthermia susceptibility via muscle baopsy and contracture testing remains controversial. 29 Contracture testing was not performed in this patient because the test is not reliable immediately after a mahgnant hyperthermia episode. 25 Authorities recommend that at least 3 months should pass between the malignant hyperthermla epasode and contracture testing. 25 Postmortem examination of skeletal muscle from patients dying of malignant hyperthermia are nonspecific, showing only extensive necrosis consistent with rhabdomyolysis, obliterating signs of preexisting malignant hyperthermia myopatby. 3° Despite counseling, the patient's close relatives decided not to undergo contraeture testing. Classic triggering agents of malignant hyperthermia are depolarizing muscle relaxants and volatile inhalation anesthetics. It is possible that malignant hyperthermia m this patient was triggered by succinylcholine administered antravenously for tracheal intubatlon. Malignant hyperthermia may have been augmented in the operating room by use of

HYPERMETABOLISM DURING CARDIOPULMONARY BYPASS

569

an anesthesia machine and breathing circuit not prepared specifically for a patient susceptible to malignant hyperthermla. 31 Malignant hyperthermia may have also been augmented in this patient by CPB. Blood catecholamine levels may increase up to 40 times baseline upon Initiation of CPB and may reach even higher levels in the immediate postoperative period. 32 Stress alone has been implicated as a possible triggering agent of malignant hyperthermia in humans.33. 34 Manifestation of malignant hyperthermia during surgery requiring CPB is extremely rare. 24-26All three case reports involved cardiac surgery. In only one was the patient considered to be malignant hyperthermia-susceptible preoperatively. 24 In all three cases, clinical signs of malignant hyperthermla occurred before CPB. Clinical signs of malignant hyperthermia exhibited during CPB included increased oxygen consumption, 24 persistent hypercarbla, 25 and resistance to systemic cooling. 24 In one case, clinical signs of malignant hyperthermia disappeared on initiation of an uneventful CPB run only to reappear after separation from CPB. 26 The use of CPB may make diagnosis of malignant hyperthermia difficult by obscuring pathognomonic clinical signs. 24-26It is unclear whether hypothermic CPB simply masks pathognomonic clinical signs of malignant hyperthermia or actually halts progression of the malignant hyperthermia episode. It is interesting to note that before availability of dantrolene, a malignant hyperthermia episode was successfully treated by initiation of partial CPB and systemic cooling for 19 minutes. 35 The only specific pharmacologic treatment for malignant hyperthermia is dantrolene, which inhibits calcium release from sarcoplasmic reticulum and reduces myoplasmIc free calcium concentration, thus causing interruption of skeletal muscle hypermetabolism. 36 Although dantrolene prophylaxis remains controversial, clearly the drug should be administered once manifestation of malignant hyperthermia occurs. 37 Untreated malignant hyperthermia has a mortality above 70%, yet with appropriate intervention, including dantrolene administration, mortality is decreased to below 10%. 28,37 Of the three case reports involving manifestation of mahgnant hyperthermia during surgery requiring CPB, two describe administration of dantrolene during CPB with subsequent disappearance of clinical signs of malignant hyperthermia (increased oxygen consumption, hypercarbia, acidosis) within 30 minutes. 24,25 In the other report, dantrolene was administered on the second postoperative day, resulting in disappearance of clinical signs of

malignant hyperthermia (hyperthermia, tachycardia, acidosis) within 60 minutes. 26All three patients survived. 24-26 Manifestation of malignant hyperthermla during surgery involving organ transplantation has been reported only twice. 22,23Both case reports involved renal transplant recipients and malignant hyperthermla in each occurred immediately before donor kidney implantation. Dantrolene was administered in each case with subsequent disappearance of clinical signs of malignant hyperthermia (hyperthermia, tachycardia, hypercarbia, acidosis) within 30 minutes. Both patients survived, and their implanted kidneys functioned properly. No information exists regarding effects of malignant hyperthermia on transplanted organs. Although effects of malignant hyperthermia on transplanted lungs are unknown, they would not be expected to be beneficial, for even after uncomplicated anesthesia and surgery, transplanted lungs are vulnerable to damage from preservation injury, reperfusion injury, volume overload, disordered fluid clearance from disrupted lymphatics, oxygen toxicity, barotrauma, anastomotic dehiscence, rejection, and infection. as Certainly, the possible addition of mahgnant hyperthermia to this milieu could not be considered advantageous. The two case reports involving renal transplant recipients, however, suggests that with appropriate intervention, including dantrolene administration, organ transplantation that occurs during malignant hyperthermia may be successful. 22,23 A possible diagnosis of malignant hyperthermia in this patient was not entertained seriously until soon after initiation of CPB. The anesthesiologist in charge of the case, however, felt comfortable excluding the diagnosis of malignant hyperthermia and thus did not administer dantrolene. It was believed that clinical signs before CPB (increased arterial carbon dioxide tension, acidosis, tachycardia) were caused by cystic fibrosis and septic shock. Absence of muscle rigidity and hyperthermia along with previous uneventful anesthetics and a negative family history also made the diagnosis of malignant hyperthermla seem unlikely. In summary, an episode of significant hypermetabolism that occurred during bilateral single-lung transplantation requiring assist of CPB has been described. Although the most likely cause of hypermetabolism in this patient was sepsis, the possibility that this scenario represented manifestation of malignant hyperthermia cannot be entirely ruled out.

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24. Quinn RD, Pae WE, McGary SA, Wickey GS. Development of malignant hyperthermla during mltral valve replacement Ann Thorac Surg 53:1114-1116, 1992 25. Kleinman B, Kalathlveetll J, Jam U. et al. Case Conference 3-1990. J Cardlothorac Vasc Anesth 4.385-399, 1990 26 MacGilhvray RG, Jann H, Vanker E, et al: Development of malignant hyperthermia obscured by cardlopulmonary bypass Can J Anaesth 33:509-514, 1986 27. Joffe M, Savage N, Sllove M- The biochemistry of malignant hyperthermia" recent concepts. Int J Blochem 24.387-398, 1992 28. Heiman-Patterson TD Neuroleptic malignant syndrome and malignant hyperthermxa. Important issues for the medical consultant Med Chn North Am 77.477-492, 1993 29. Larach MG: Should we use muscle biopsy to diagnose malignant hyperthermla susceptlblhty9 Anesthesiology 79:1-4, 1993 30 Harriman DGF' Malignant hyperthermia myopathy--A critical review. Br J Anaesth 60:309-316, 1988 31 Beebe JJ, Sessler DI' Preparation of anesthesia machines for patients susceptible to malignant hyperthermia Anesthesiology 69'395-400, 1988 32. Spelght KL: Perioperatlve stress response suppression in cardlothoracIc surgery, In Gravlee GP, Rauck RL (eds): Pain Management in Cardlothoraclc Surgery, A Society of Cardiovascular Anesthesiologists Monograph. Philadelphia, PA, Llpplncott, 1993, pp 169-199 33. Pollock N, Hodges M, Sendall J Prolonged mahgnant hyperthermia In the absence of triggering agents Anaesth Int Care 20:520-523, 1992 34 Grlnberg R, Edehst G, Gordon A Postoperative malignant byperthermla episodes in patients who recewed "safe" anaesthetics. Can J Arlaesth 30'273-276, 1983 35 Ryan JF, Donlon JV, Malt RA, et al: Cardlopulmonary bypass in the treatment of malignant hyperthermla N Engl J Med 290:1121-1122, 1974 36 Lopez JR, Gerardi A, Lopez MJ, et al: Effects of dantrolene on myoplasmic free [Ca2+] measured m vivo In patients susceptible to malignant hyperthermia. Anesthesiology 76-711-719, 1992 37. Kolb ME, Horne ML, Martz R: Dantrolene in human malignant hyperthermm; a multicenter study. Anesthesiology 56' 254-262, 1982 38. Blerman MI, Stem KL, Stuart RS, et al' Critical care management of lung transplant recipients J Int Care Med 6 135142, 1991