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A fulminant malignant hyperthermia episode during laparoscopic donor nephrectomy – Case report
i n d i a n j o u r n a l o f t r a n s p l a n t a t i o n 7 ( 2 0 1 3 ) 9 4 e9 6
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/ijt
Case Report
A fulminant malignant hyperthermia episode during laparoscopic donor nephrectomy e Case report Chinnamuthu Murugesan*, Bandlapally Ramanjaneya Gupta Harish, Surjya Kanta Mohanty, Prashanth Kulkarni Department of Anaesthesiology and Urology, Narayana Hrudayalaya Institute of Medical Sciences, Bangalore, Karnataka, India
article info
abstract
Article history:
Malignant hyperthermia (MH) is a rare life threatening complication during general
Received 11 March 2013
anaesthesia using volatile anaesthetic agents. We report a case of fulminant MH episode
Accepted 10 May 2013
during laparoscopic donor nephrectomy. The early clinical manifestations include rapid
Available online 14 July 2013
rise of ETCO2, respiratory acidosis and tachycardia, later fever, generalized muscle rigidity, hyperkalemia and severe rhabdomyolysis were noted. An acute MH was diagnosed and
Keywords:
prompt resuscitative measures were initiated. No intravenous dantrolene was available for
Malignant hyperthermia
administration. Our patient survived of this acute fulminant MH due to early diagnosis,
Hyperkalemia
coordinated teamwork and availability of other resuscitative modalities only possible in a
Rhabdomyolysis
large tertiary care centre.
Respiratory acidosis
1.
Copyright ª 2013, Indian Society of Organ Transplantation. All rights reserved.
Introduction
Malignant hyperthermia (MH) is a rare pharmacogenetic disorder characterised by increased expired carbon dioxide, muscle rigidity, tachycardia and fever, which occur following the exposure with volatile anaesthetic agents and succinylcholine.1e3 Early diagnosis was critical for successful outcome of the patient.
2.
Case report
A 22-year old African male soccer player was evaluated for a voluntary donor nephrectomy. There was no history of neuromuscular disorders, malignant hyperthermia (MH),
or other anaesthesia-related complications in the patient or other family members. He did not have history of drug abuse, known drug allergies and co-morbidities. The patient weighed 75 kg and his body mass index was 24.5 kg/m2. His preoperative blood investigations were unremarkable. In the operating room, standard monitors were used including noninvasive blood pressure cuff, five lead electrocardiogram, pulse oximeter and capnography. Patient was anaesthetised with propofol (100 mg) and fentanyl (100 mg); neuromuscular blockade was achieved with vecuronium (8 mg). An 8.5 mm size endotracheal tube was used for tracheal intubation without difficulty. Anaesthesia was maintained with oxygen, air, isoflurane, intermittent boluses of fentanyl and vecuronium. After induction of anaesthesia a radial arterial catheter, central venous catheter and nasopharyngeal temperature
* Corresponding author. Tel.: þ91 9980553940 (mobile). E-mail address: [email protected] (C. Murugesan). 2212-0017/$ e see front matter Copyright ª 2013, Indian Society of Organ Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.ijt.2013.05.007
95
i n d i a n j o u r n a l o f t r a n s p l a n t a t i o n 7 ( 2 0 1 3 ) 9 4 e9 6
probe were inserted. The laparoscopic procedure began with the patient in right lateral decubitus position using carbon dioxide (CO2) pneumoperitoneum and the intraabdominal pressure was maintained at 14 mmHg. After 2.5 h of post induction and just prior to clamping of renal vessels, the end tidal carbon dioxide (ETCO2) was gradually increased from 35 mmHg to 50 mmHg. His heart rate was 104 beats/minute and temperature was 36.8 C at that time. Chest auscultation revealed equal bilateral breath sounds with no wheezing. A careful check up of anaesthesia machine and circuit revealed no air leaks. The minute ventilation was increased to 8 L/ minute from 6 L/minute. Despite this, the ETCO2 was continued to increase from 50 mmHg to 70 mmHg over the next 20 min. The pneumoperitoneum was released and the surgery was temporarily stopped assuming that the rise of ETCO2 as a result of CO2 insufflation. At that time, an arterial blood gas analysis (ABG) revealed profound respiratory acidosis (Table 1 and Fig. 1). Subsequently, it was noted that there was a progressive rise of nasopharyngeal temperature at the rate of 0.5 C/5 min associated with tachycardia (120/min). Rapidly increasing ETCO2, fever, tachycardia suggested a physiologic perturbation that required immediate attention and investigation. It was now decided to place the patient supine and noticed significant muscle rigidity involving all over the body. An acute malignant hyperthermia (MH) was diagnosed and prompt resuscitative measures were initiated (see Table 1 and Fig. 1 for data). Consequently, a repeat ABG showed worsening of respiratory acidosis (Table 1, 170 min). In spite of resuscitative measures the nasopharyngeal temperature was peaked at 42.4 C over next 25 min. The resuscitative measures include, immediate discontinuation of isoflurane, starting of intravenous propofol infusion, hyperventilation of lungs with 100% O2, and use of a new anaesthesia machine without vapourisers. Cooling measures initiated instantaneously which include surface cooling with ice packs, gastric and bladder lavage with ice-cold saline. Cold intravenous fluids were infused. No intravenous dantrolene was available for administration. Meanwhile, the patient developed severe hypotension (48/ 26 mmHg), bradycardia, nodal rhythm and ventricular ectopics. An infusion of dopamine (5 mg/kg/min) and noradrenaline (0.2 mg/kg/min) were initiated to stabilise the haemodynamic derangement. Subsequent ABG revealed severe
hyperkalemia (K-6.4 mmol/L), which was vigorously treated with a 50 ml bolus dose and continuous infusion of sodium bicarbonate (8.4%). A continuous infusion of dextrose (50%) with insulin (20 units) was also initiated to treat the hyperkalemia with close monitoring of blood glucose levels. A bolus dose of frusemide-80 mg was administered along with adequate hydration (the urine was cola coloured). After 2 h of resuscitation, the elevated ETCO2 and body temperature began to fall, the muscle rigidity was improved and the patient showed improvement in haemodynamics. Eventually the surgical procedure was terminated and laparoscopic port incisions were closed. The patient was transferred to the intensive care unit with inotropic support. Postoperatively, ETCO2 and core temperature were monitored in the ICU and the inotropic support was gradually weaned. Oral dantrolene therapy was initiated at the dose of 4 mg/kg TID via nasogastric tube and stopped after 48 h due to elevation of liver enzymes. An additional spike in temperature (38 C) during the first 12 h of the ICU stay was treated with cold tepid sponging and cold intravenous fluids. The patient remained sedated with propofol (100e150 mg/h) for 40 h in the ICU following which he was weaned and extubated. Hydration, diuretic use and alkalinisation were continued during the ICU stay to ensure 2 ml/kg/h of urine output which was cola coloured for 9 days. His plasma creatine phosphokinase was peaked at 2,86,800 IU/L on 5th postoperative day (Fig. 1) and was accompanied by a transient increase in serum creatinine (1.7 mg/dl), D-dimer (3.3 mg/dl), and INR (1.61) during the first 48 h in the ICU. The patient was discharged from the hospital 10 days after the occurrence of malignant hyperthermia. A genetic test was done at University of Pittsburg which revealed an EMHG-registered disease associated mutation (p.Gly341Arg). A rare nonpathogenic polymorphism (heterozygous c. 14647-36 >A, intron 101, rs 114134909) was observed in this patient, which infrequently reported from a West African population. The family members were counselled about potential risk of MH susceptibility.
3.
Discussion
MH is a rare life threatening complication during general anaesthesia using volatile anaesthetic agents. Though its
Table 1 e Results of arterial blood gas analysis. Time(Min) pH PaO2 (mmHg) PaCO2 (mmHg) Base Excess (mmol/L) Kþ (mmol/L) FIO2 ETCO2
Baseline
150 Mina
170 Min
210 Min
220 Min
250 Min
260 Minb
285 Min
7.43 255 36.3 0.3 3.7 0.5 30
7.17 165 80 1.6 4.56 0.5 75
6.98 329 143 2.5 4.68 1.0 Not recordable
7.00 372 110 7.5 6.43 1.0 Not recordable
6.96 332 114 9.2 6.2 1.0 Not recordable
7.09 398 91 4.2 6.44 1.0 81
7.20 453 66 3.5 5.77 1.0 63
7.32 237 47 2.6 5.48 0.5 40
Time in minutes after induction of anaesthesia. PaO2 ¼ Partial pressure of oxygen; PaCo2 ¼ Partial pressure of carbon dioxide; Kþ ¼ Potassium; FIO2 ¼ Fraction of inspiratory oxygen. a The early signs of MH (Hypercarbia, respiratory acidosis and tachycardia) were noted noted after 150 min of anaesthesia induction. b Response to resuscitative measures.
96
i n d i a n j o u r n a l o f t r a n s p l a n t a t i o n 7 ( 2 0 1 3 ) 9 4 e9 6
Fig. 1 e Left figure shows increasing end tidal carbon dioxide (ETCO2) and nasopharyngeal temperature in relation to time during the surgery and right figure shows trends of CPK (IU/L) following malignant hyperthermia episode.
incidence among Indian population is not known, it may be as low as 1:250,000 anaesthetics among African population.4 The present case is unusual in few perspectives. First, the diagnosis of MH during laparoscopic donor nephrectomy may be difficult because the early signs of disease are similar to the expected physiological changes that occur during laparoscopy. Second, the decrease in body temperature with CO2 insufflation can potentially mask symptoms of MH and this may result in delaying the diagnosis. Finally, the role of CO2 pneumoperitoneum in triggering the onset and severity of MH in susceptible individuals yet to be demonstrated. The diagnosis of MH in the present case was made on clinical presentation during the laparoscopic nephrectomy surgery. The early clinical manifestations were a rapid rise of ETCO2, respiratory acidosis and tachycardia, later fever, generalized muscle rigidity, hyperkalemia and rhabdomyolysis (elevated creatine phosphokinase, cola coloured urine) were noted. According to clinical grading scale described by Larach et al, the total score in our patient was 73 indicating the diagnosis of MH was almost certain.5 Progressively increasing ETCO2 is an ominous sign of MH, however CO2 pneumoperitoneum as in the current case may increase ETCO2 during the starting of the surgery. Other common cause for elevation of ETCO2 after 30 min of beginning of laparoscopic nephrectomy is CO2 subcutaneous emphysema. This diagnosis was ruled out because of negative examination of local swelling and crepitus. Massive CO2 embolism was ruled out by increasing ETCO2, absence of desaturation, millwheel murmur and hypotension.6 The delayed rise of body temperature in the present case (temperature was 38 C when ETCO2 was 90 mmHg) in relation with ETCO2 may be attributed with masking effect of CO2 pneumoperitoneum (Fig. 1). As intra-
venous dantrolene is the treatment of choice for patients with MH, its paucity of availability need to be addressed.
4.
Conclusion
Unawareness of MH and cost are the main factors for not stocking intravenous dantrolene. Our patient survived of this acute fulminant MH due to early diagnosis, coordinated teamwork and availability of other resuscitative modalities.
Conflicts of interest All authors have none to declare.
references
1. Wilson RD, Dent TE, Traber DL, McCoy NR, Allen CR. Malignant hyperthermia with anesthesia. JAMA. 1967;202(3):183e186. 2. Denborough MA, Lovell R. Anaesthetic deaths in a family. Lancet. 1960;2:45. 3. Levitt RC. Prospects for the diagnosis of malignant hyperthermia susceptibility using molecular genetic approaches. Anesthesiology. 1992;76:1039e1048. 4. Lombard TP, Couper JL. Malignant hyperthermia in a black adolescent. S Afr Med J. 1988;73:726e729. 5. Larach MG, Localio AR, Allen GC, et al. A clinical grading scale to predict malignant hyperthermia susceptibility. Anesthesiology. 1994;80:771e779. 6. Wahba RW, Tessler MJ, Kleiman SJ. Acute ventilatory complications during laparoscopic upper abdominal surgery. Can J Anaesth. 1996;43:77.
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/ijt
Case Report
A fulminant malignant hyperthermia episode during laparoscopic donor nephrectomy e Case report Chinnamuthu Murugesan*, Bandlapally Ramanjaneya Gupta Harish, Surjya Kanta Mohanty, Prashanth Kulkarni Department of Anaesthesiology and Urology, Narayana Hrudayalaya Institute of Medical Sciences, Bangalore, Karnataka, India
article info
abstract
Article history:
Malignant hyperthermia (MH) is a rare life threatening complication during general
Received 11 March 2013
anaesthesia using volatile anaesthetic agents. We report a case of fulminant MH episode
Accepted 10 May 2013
during laparoscopic donor nephrectomy. The early clinical manifestations include rapid
Available online 14 July 2013
rise of ETCO2, respiratory acidosis and tachycardia, later fever, generalized muscle rigidity, hyperkalemia and severe rhabdomyolysis were noted. An acute MH was diagnosed and
Keywords:
prompt resuscitative measures were initiated. No intravenous dantrolene was available for
Malignant hyperthermia
administration. Our patient survived of this acute fulminant MH due to early diagnosis,
Hyperkalemia
coordinated teamwork and availability of other resuscitative modalities only possible in a
Rhabdomyolysis
large tertiary care centre.
Respiratory acidosis
1.
Copyright ª 2013, Indian Society of Organ Transplantation. All rights reserved.
Introduction
Malignant hyperthermia (MH) is a rare pharmacogenetic disorder characterised by increased expired carbon dioxide, muscle rigidity, tachycardia and fever, which occur following the exposure with volatile anaesthetic agents and succinylcholine.1e3 Early diagnosis was critical for successful outcome of the patient.
2.
Case report
A 22-year old African male soccer player was evaluated for a voluntary donor nephrectomy. There was no history of neuromuscular disorders, malignant hyperthermia (MH),
or other anaesthesia-related complications in the patient or other family members. He did not have history of drug abuse, known drug allergies and co-morbidities. The patient weighed 75 kg and his body mass index was 24.5 kg/m2. His preoperative blood investigations were unremarkable. In the operating room, standard monitors were used including noninvasive blood pressure cuff, five lead electrocardiogram, pulse oximeter and capnography. Patient was anaesthetised with propofol (100 mg) and fentanyl (100 mg); neuromuscular blockade was achieved with vecuronium (8 mg). An 8.5 mm size endotracheal tube was used for tracheal intubation without difficulty. Anaesthesia was maintained with oxygen, air, isoflurane, intermittent boluses of fentanyl and vecuronium. After induction of anaesthesia a radial arterial catheter, central venous catheter and nasopharyngeal temperature
* Corresponding author. Tel.: þ91 9980553940 (mobile). E-mail address: [email protected] (C. Murugesan). 2212-0017/$ e see front matter Copyright ª 2013, Indian Society of Organ Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.ijt.2013.05.007
95
i n d i a n j o u r n a l o f t r a n s p l a n t a t i o n 7 ( 2 0 1 3 ) 9 4 e9 6
probe were inserted. The laparoscopic procedure began with the patient in right lateral decubitus position using carbon dioxide (CO2) pneumoperitoneum and the intraabdominal pressure was maintained at 14 mmHg. After 2.5 h of post induction and just prior to clamping of renal vessels, the end tidal carbon dioxide (ETCO2) was gradually increased from 35 mmHg to 50 mmHg. His heart rate was 104 beats/minute and temperature was 36.8 C at that time. Chest auscultation revealed equal bilateral breath sounds with no wheezing. A careful check up of anaesthesia machine and circuit revealed no air leaks. The minute ventilation was increased to 8 L/ minute from 6 L/minute. Despite this, the ETCO2 was continued to increase from 50 mmHg to 70 mmHg over the next 20 min. The pneumoperitoneum was released and the surgery was temporarily stopped assuming that the rise of ETCO2 as a result of CO2 insufflation. At that time, an arterial blood gas analysis (ABG) revealed profound respiratory acidosis (Table 1 and Fig. 1). Subsequently, it was noted that there was a progressive rise of nasopharyngeal temperature at the rate of 0.5 C/5 min associated with tachycardia (120/min). Rapidly increasing ETCO2, fever, tachycardia suggested a physiologic perturbation that required immediate attention and investigation. It was now decided to place the patient supine and noticed significant muscle rigidity involving all over the body. An acute malignant hyperthermia (MH) was diagnosed and prompt resuscitative measures were initiated (see Table 1 and Fig. 1 for data). Consequently, a repeat ABG showed worsening of respiratory acidosis (Table 1, 170 min). In spite of resuscitative measures the nasopharyngeal temperature was peaked at 42.4 C over next 25 min. The resuscitative measures include, immediate discontinuation of isoflurane, starting of intravenous propofol infusion, hyperventilation of lungs with 100% O2, and use of a new anaesthesia machine without vapourisers. Cooling measures initiated instantaneously which include surface cooling with ice packs, gastric and bladder lavage with ice-cold saline. Cold intravenous fluids were infused. No intravenous dantrolene was available for administration. Meanwhile, the patient developed severe hypotension (48/ 26 mmHg), bradycardia, nodal rhythm and ventricular ectopics. An infusion of dopamine (5 mg/kg/min) and noradrenaline (0.2 mg/kg/min) were initiated to stabilise the haemodynamic derangement. Subsequent ABG revealed severe
hyperkalemia (K-6.4 mmol/L), which was vigorously treated with a 50 ml bolus dose and continuous infusion of sodium bicarbonate (8.4%). A continuous infusion of dextrose (50%) with insulin (20 units) was also initiated to treat the hyperkalemia with close monitoring of blood glucose levels. A bolus dose of frusemide-80 mg was administered along with adequate hydration (the urine was cola coloured). After 2 h of resuscitation, the elevated ETCO2 and body temperature began to fall, the muscle rigidity was improved and the patient showed improvement in haemodynamics. Eventually the surgical procedure was terminated and laparoscopic port incisions were closed. The patient was transferred to the intensive care unit with inotropic support. Postoperatively, ETCO2 and core temperature were monitored in the ICU and the inotropic support was gradually weaned. Oral dantrolene therapy was initiated at the dose of 4 mg/kg TID via nasogastric tube and stopped after 48 h due to elevation of liver enzymes. An additional spike in temperature (38 C) during the first 12 h of the ICU stay was treated with cold tepid sponging and cold intravenous fluids. The patient remained sedated with propofol (100e150 mg/h) for 40 h in the ICU following which he was weaned and extubated. Hydration, diuretic use and alkalinisation were continued during the ICU stay to ensure 2 ml/kg/h of urine output which was cola coloured for 9 days. His plasma creatine phosphokinase was peaked at 2,86,800 IU/L on 5th postoperative day (Fig. 1) and was accompanied by a transient increase in serum creatinine (1.7 mg/dl), D-dimer (3.3 mg/dl), and INR (1.61) during the first 48 h in the ICU. The patient was discharged from the hospital 10 days after the occurrence of malignant hyperthermia. A genetic test was done at University of Pittsburg which revealed an EMHG-registered disease associated mutation (p.Gly341Arg). A rare nonpathogenic polymorphism (heterozygous c. 14647-36 >A, intron 101, rs 114134909) was observed in this patient, which infrequently reported from a West African population. The family members were counselled about potential risk of MH susceptibility.
3.
Discussion
MH is a rare life threatening complication during general anaesthesia using volatile anaesthetic agents. Though its
Table 1 e Results of arterial blood gas analysis. Time(Min) pH PaO2 (mmHg) PaCO2 (mmHg) Base Excess (mmol/L) Kþ (mmol/L) FIO2 ETCO2
Baseline
150 Mina
170 Min
210 Min
220 Min
250 Min
260 Minb
285 Min
7.43 255 36.3 0.3 3.7 0.5 30
7.17 165 80 1.6 4.56 0.5 75
6.98 329 143 2.5 4.68 1.0 Not recordable
7.00 372 110 7.5 6.43 1.0 Not recordable
6.96 332 114 9.2 6.2 1.0 Not recordable
7.09 398 91 4.2 6.44 1.0 81
7.20 453 66 3.5 5.77 1.0 63
7.32 237 47 2.6 5.48 0.5 40
Time in minutes after induction of anaesthesia. PaO2 ¼ Partial pressure of oxygen; PaCo2 ¼ Partial pressure of carbon dioxide; Kþ ¼ Potassium; FIO2 ¼ Fraction of inspiratory oxygen. a The early signs of MH (Hypercarbia, respiratory acidosis and tachycardia) were noted noted after 150 min of anaesthesia induction. b Response to resuscitative measures.
96
i n d i a n j o u r n a l o f t r a n s p l a n t a t i o n 7 ( 2 0 1 3 ) 9 4 e9 6
Fig. 1 e Left figure shows increasing end tidal carbon dioxide (ETCO2) and nasopharyngeal temperature in relation to time during the surgery and right figure shows trends of CPK (IU/L) following malignant hyperthermia episode.
incidence among Indian population is not known, it may be as low as 1:250,000 anaesthetics among African population.4 The present case is unusual in few perspectives. First, the diagnosis of MH during laparoscopic donor nephrectomy may be difficult because the early signs of disease are similar to the expected physiological changes that occur during laparoscopy. Second, the decrease in body temperature with CO2 insufflation can potentially mask symptoms of MH and this may result in delaying the diagnosis. Finally, the role of CO2 pneumoperitoneum in triggering the onset and severity of MH in susceptible individuals yet to be demonstrated. The diagnosis of MH in the present case was made on clinical presentation during the laparoscopic nephrectomy surgery. The early clinical manifestations were a rapid rise of ETCO2, respiratory acidosis and tachycardia, later fever, generalized muscle rigidity, hyperkalemia and rhabdomyolysis (elevated creatine phosphokinase, cola coloured urine) were noted. According to clinical grading scale described by Larach et al, the total score in our patient was 73 indicating the diagnosis of MH was almost certain.5 Progressively increasing ETCO2 is an ominous sign of MH, however CO2 pneumoperitoneum as in the current case may increase ETCO2 during the starting of the surgery. Other common cause for elevation of ETCO2 after 30 min of beginning of laparoscopic nephrectomy is CO2 subcutaneous emphysema. This diagnosis was ruled out because of negative examination of local swelling and crepitus. Massive CO2 embolism was ruled out by increasing ETCO2, absence of desaturation, millwheel murmur and hypotension.6 The delayed rise of body temperature in the present case (temperature was 38 C when ETCO2 was 90 mmHg) in relation with ETCO2 may be attributed with masking effect of CO2 pneumoperitoneum (Fig. 1). As intra-
venous dantrolene is the treatment of choice for patients with MH, its paucity of availability need to be addressed.
4.
Conclusion
Unawareness of MH and cost are the main factors for not stocking intravenous dantrolene. Our patient survived of this acute fulminant MH due to early diagnosis, coordinated teamwork and availability of other resuscitative modalities.
Conflicts of interest All authors have none to declare.
references
1. Wilson RD, Dent TE, Traber DL, McCoy NR, Allen CR. Malignant hyperthermia with anesthesia. JAMA. 1967;202(3):183e186. 2. Denborough MA, Lovell R. Anaesthetic deaths in a family. Lancet. 1960;2:45. 3. Levitt RC. Prospects for the diagnosis of malignant hyperthermia susceptibility using molecular genetic approaches. Anesthesiology. 1992;76:1039e1048. 4. Lombard TP, Couper JL. Malignant hyperthermia in a black adolescent. S Afr Med J. 1988;73:726e729. 5. Larach MG, Localio AR, Allen GC, et al. A clinical grading scale to predict malignant hyperthermia susceptibility. Anesthesiology. 1994;80:771e779. 6. Wahba RW, Tessler MJ, Kleiman SJ. Acute ventilatory complications during laparoscopic upper abdominal surgery. Can J Anaesth. 1996;43:77.