Case report
Suspected malignant hyperthermia in a child
with laminin a2(merosin)deficiency in the absence of a triggering agent
MOHANAD SHUKRY M D*,ZURAB V GURULI M D P h D†
AND USHA RAMADHYANI M B B S†
*Oklahoma University Health Sciences Center⁄Children’s Hospital,Oklahoma City,OK and
†Department of Anesthesiology,Tulane University Health Sciences Center,New Orleans,LA,
USA
Summary
Malignant hyperthermia(MH)is an inherited disorder of the skeletaluneventful
muscles that can be triggered by many anesthetic agents.MH has
different presentations and manifestations that makes it difficult to
diagnose.Patients with laminin a2deficiency have never been
reported to be susceptible to MH.We present a suspected MH episode
in the absence of classic triggering agents in a7-year-old boy with
laminin a2(merosin)deficiency and congenital muscular dystrophy.
The episode was diagnosed using the MH clinical grading scale and
responded well to prompt management with dantrolene.We conclude
that patients with laminin a2deficiency may be susceptible to MH,
and early suspicion and rapid treatment is vital in the management of
MH.Anesthesiologists should be prepared to treat MH in susceptible
patients even in the absence of a classical triggering agent.
Keywords:malignant hyperthermia;laminin a2(merosin)deficiency;
congenital muscular dystrophy;dexmeditomidine
Introduction
Malignant hyperthermia(MH)is the name given to a severe reaction during general anesthesia(GA)that wasfirst described in1960(1).It is considered a pharmacogenetic disease where halogenated agents and succinylcholine are deemed to be the classical ‘triggering agents’.Patients with laminin a2(meros-in)deficiency have never been reported to be susceptible to MH.However,patients with various musculoskeletal abnormalities such as scoliosis and muscular dystrophy are reported to be at increased risk of MH compared with the general surgical population(2).The muscle of MH susceptible(MHS) individual often appears to be normal in the absence of a‘triggering agent’.
We present a suspected episode of MH in a7-year-old boy with laminin a2deficiency and severe congenital muscular dystrophy(CMD)who did not receive any of the classic triggering agents and responded well to dantrolene.
Case Report
A7-year-old male child,weighing22kg and with a height of68cm,with laminin a2deficiency and classic CMD phenotype,rigid spine syndrome,and severe scoliosis presented for posterior spinal fusion.
Correspondence to:Dr M.Shukry,Department of Anesthesiology,
OUHSC⁄Children’s Hospital,940NE13th St,4B4200,Oklahoma
City,OK73104,USA(email:mohanad-shukry@ouhsc.edu).
Pediatric Anesthesia200616:462–465doi:10.1111/j.1460-9592.2005.01742.x 462Ó2005Blackwell Publishing Ltd
His past medical history was significant for chronic mild respiratory insufficiency requiring bilevel pos-itive airway pressure(BIPAP)therapy.He had repeatedly received general inhalational anesthetic at an outside institution for different procedures such as Nissen fundoplication,muscle and nerve biopsy,and heel-cord lengthening.During the last procedure,he underwent a difficult traumatic direct laryngoscopy and tracheal intubation that injured his left upper incisor.On physical examination,he was sitting in a wheelchair,appeared very thin,but was able to support his head which wasfixed to the right.Muscular contracture or increased muscular tone were not noted,and his mental status was intact as he appropriately responded to all questions concerning his medical problems.
On the day of surgery,the precautions recom-mended by the Malignant Hyperthermia Associ-ation of US for MHS patients were taken;the halogenated agent vaporizers were removed from the anesthesia machine,the breathing circuit was flushed with oxygen for15min,and the soda lime canisters were replaced with fresh new ones.The patient’s central line was sterilely accessed and2mg of midazolam was administered.Standard Ameri-can Society of Anesthesiology monitors were ap-plied and dexmedetomidine was infused to facilitate sedatedfiberoptic tracheal intubation.Tracheal in-tubation was performed at thefirst attempt using the Shikani Optical Stylet TM(Clarus Medical,Minne-apolis,MN,USA)followed by the administration of rocuronium(0.5mgÆkg)1).The right radial artery was cannulated,and peripheral intravenous access was sited where total intravenous general anesthesia (TIVA)was maintained with sufentanil(0.004ugÆkg)1Æmin)1)and propofol(100ugÆkg)1Æmin)1).An esophageal probe was inserted to monitor body temperature,and a Bair HuggerÒwarming blanket (Augustine Medical,Eden Prairie,MN,USA)was used to maintain normothermia.A Foley catheter (BardexÒ,  C.R.Bard.Inc.,Covington,GA)was inserted,and the patient was turned into the prone position.Vital signs remained stable throughout the procedure that lasted4h and required transfusion of4units of packed red blood cells and1unit of fresh frozen plasma with adequate urine output of 875ml.Following closure of the incision and while applying the surgical dressing(sufentanil and prop-ofol were still administered at the same infusion rate,and mean arterial blood pressure(BP)and heart ra
te(HR)were stable for the last45min at 80–89mmHg and120bÆmin)1,respectively),peak inspiratory pressure(PIP)increased from32to 43cmH2O(Table1).Thirty milligrams of propofol and10mg of rocuronium were administered and the patient was returned to supine position in preparation for transfer to the pediatric intensive care unit(PICU).At that time,severe total body rigidity including the extremities was noted,and arterial systolic BP dropped over few minutes(from 132to72mmHg)while HR increased from120to 160.Simultaneously,endtidal carbon dioxide(P E CO2) rose from4.2to6.6kPa(32–51mmHg)with a slight elevation in esophageal temperature(36.7°C–38°C). MH was suspected and2.5mgÆkg)1dantrolene was administered promptly.In addition,fresh gasflow and fraction of inspired oxygen were increased to 10lÆmin)1and100%respectively,and20mlÆkg)1of
Table1
Intraoperative laboratory values at different time points
Time(minutes)
Variables060105180215250300PICU pH7.427.427.467.317.347.277.357.32 P CO2(mmHg)4040353545404046
P O2(mmHg)564584550577576531457281 HCO3(mmolÆl)1)2627252123182322 BE(mmolÆl)1)222)5)3)9)3)2.9 K(mmolÆl)1)  3.2  3.34  3.95  5.8  4.2  3.4 T°(C)35.835.636.636.736.937.93736.6 PIP(cmH2O)1922243231423214 PICU,pediatric intensive care unit;BE,base excess;K,potassium;T,temperature;PIP,positive intrathoracic pressure.
0:after induction,bold:first values after the suspected malignant hyperthermia episode.
SUSPECTED MALIGNANT HYPERTHERMIA463Ó2005Blackwell Publishing Ltd,Pediatric Anesthesia,16,462–465
normal saline was administered.An arterial blood gas(ABG)obtained a few minutes later showed moderate metabolic acidosis with moderately eleva-ted serum potassium level(Table1);2mmolÆkg)1of sodium bicarbonate was administered.Five minutes later,body rigidity was still noticeable and BP did not improve,so dantrolene was readministered over 15min to a total of10mgÆkg)1.After15min,body rigidity improved and HR stabilized in130–139 bÆmin)1and PIP decreased to31cmH2O.Moreover, ABG values showed improvement in the acidosis and serum potassium levels(Table1).The patient was then transported intubated to the PICU and his blood gas values normalized.Although serum cre-atine kinase(CK)level was686UÆl)1on admission to PICU(normal values22–200UÆl)1),it increased to2268
UÆl)1the following day and gradually decreased within few days without the development of myoglobinuria;preoperative CK values were not available.
Vital signs remained stable in the PICU without administration of extra doses of dantrolene,and the trachea was extubated2days later.Before hospital discharge,the suspected syndrome was explained to the patient and his adopted parents and he was advised to undergo a muscle biopsy and contracture test to confirm the susceptibility.In addition,he was provided with a letter explaining our perioperative management for future reference.
Discussion
This was a7-year-old boy with laminin a2deficiency and CMD who developed manifestations of MH that responded to dantrolene.Although not all myopathic patients are MHS,presence of a known or suspected myopathy should alert the anesthesiologist to the increased potential for MH susceptibility and/or conditions that may mimic MH(3).This patient developed signs and symptoms of MH without exposure to classical‘triggering agents’.The fact that he was exposed to halogenated agents for prior surgery without complications is non-contributory as previous uneventful exposures to MH triggering agent does not exclude the susceptibility(4).Thefirst sign he exhibited was an elevated PIP,which was i
nitially diagnosed as light anesthesia and treated with a dose of propofol and muscle relaxant.How-ever,when severe muscular rigidity and increased sympathetic discharge were noted in spite of treating ‘light GA’,MH was suspected and treated promptly. Neuroleptic malignant syndrome and acute lethal catatonia may exhibit the same symptoms(rigidity and hemodynamic instability),however the fact that the patient was not taking any antipsychotic agent preoperatively made these diagnoses unlikely(5). Hypovolemia may also present with hypotension and tachycardia,especially upon switching the patient’s position from prone to supine.However, rigidity is not a sign of hypovolemia.
Allergic reaction could present with the same manifestations and should be considered in the differential diagnosis particularly when the patient had received a neuromuscular blocking agent.Ro-curonium has been increasingly reported to cause allergic reaction under anesthesia with different degrees and manifestations.Bronchospasm could be the only symptom in some cases,but severe hemodynamic instability and respiratory distress syndrome could lead to death in other cases even when treated appropriately(6).Our patient received multiple doses of rocuronium before the episode without any complication and recovered without receiving any vasoactive medications such as epi-nephrine,which made us exclude allergic reaction as the primary diagnosis.
Part of the problem in diagnosing MH is the absence of a specific clinical feature.MH can present with
mild signs or symptoms such as moderate increase in HR and BP with a slight metabolic or respiratory acidosis(3).Fever is an inconsistent and often late sign,and CK levels may increase moder-ately and could continue to rise for8–20h(7).While mild CK elevation could be a result of laminin a2 deficiency,surgical destruction of the muscles or MH,early treatment with dantrolene in this case could have prevented CK from reaching extremely high levels:CK level>10,000UÆl)1is considered a positivefinding that is consistent with MH(3). The MH clinical grading scale,which was estab-lished in1994by an MH expert panel,is intended to assist MH researchers in classifying adverse events that occur within24h of the administration of an anesthetic(8).Using this scale,our patient scored63 points;15for generalized muscular rigidity,15for inappropriate hypercarbia,15for inappropriate rapid increase in temperature,three for inappropri-ate sinus tachycardia,10for arterial base excess
464M.SHUKRY ET AL.
Ó2005Blackwell Publishing Ltd,Pediatric Anesthesia,16,462–465
more negative than)8mmolÆl)1,andfive for rapid reversal of MH signs of metabolic acidosis with dantrolene.A score over50on this scale can be interpreted as an episode of‘almost certain MH’(8). Additionally,this score could have been underesti-mated in our patient as his biological family history w
as inaccessible because of his adoption. Mutations in the gene(RYR1)encoding the skeletal muscle calcium release channel(ryanodine receptor protein RyR1)are linked to MH susceptibility in humans(9).However,mutations in RYR1have not been identified in all MH families.The adverse reaction in this patient did not occur from ryanodine receptors mutation,but clearly because of muscle cell weakness for different reasons.Laminin a2muta-tions have never been studied or reported as a possible cause of MH and patients with laminin a2 mutations may not have classical CMD phenotype (10).This could be an area worthy of research in MH. Halogenated anesthetic agents and depolarizing muscle relaxants are the classic pharmacological triggers of MH,but cases of MH under GA have been reported without the exposure to any of these drugs(2).Except for dexmedetomidine,there is vast experience of the safe use of the more commonly used i.v.anesthetic drugs in patients who are known to be MHS(4).However,there is no report indicating that dexmedetomidine could be a triggering agent. This case emphasizes again that early invest-igation and treatment is the key in the management of MH.However,it is unique in the fact that laminin a2mutations have never been studied or reported as a possible cause of MH.Avoiding halogenated agents in these patients may not be the answer to preventing MH and anesthesiologists should be prepared to treat MH in susceptible patients even in the presence of TIVA.Source offinancial support Departmental.
Acknowledgements
The authors thank Bobby D.Nossaman,MD(Asso-ciate Professor,Anesthesiology,Tulane University Medical School,New Orleans,LA,USA)and Barbra W.Brandom,MD(Professor,Anesthesiology,Chil-dren’s Hospital of Pittsburgh)for their critical review of the manuscript.
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Accepted28April2005
SUSPECTED MALIGNANT HYPERTHERMIA465Ó2005Blackwell Publishing Ltd,Pediatric Anesthesia,16,462–465

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