Volumen 16 Número 4 Octubre - Diciembre 2004

 

Case Report

Spinal Ropivacaine in Safe in Malignant Hyperthermia. A Case Report

Victor Whizar-Lugo MD*
Roberto Cisneros-Corral MD*
Jaime Campos-León MD**
Juan C. Carrillo-Flores***

First author address:
Anestesiología y Medicina del Dolor. Centro Médico del Noroeste. Calle Misión de San Diego 2993-306. Zona Río Tijuana. Tijuana B.C., México 22320. vwhizar@anestesia-dolor.org   www.anestesia-dolor.org

 



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* Anestesiología y Medicina del Dolor
Centro Médico del Noroeste
Tijuana, B.C., México 

** Plastic Surgeon
COSMED
Centro Médico del Noroeste
Tijuana, B.C., México

*** Medical Student
Facultad de Medicina
Universidad Autónoma de Baja California
Tijuana, B.C., México



Abstract

We report a case of malignant hyperthermia susceptible Mexican female patient undergoing breast augmentation and abdominal liposculpture. Spinal anesthesia with hyperbaric ropivacaine-clonidine was performed without dantrolene prophylaxis. There were no complications during or after surgery. Our case is in concordance with others authors that neuroaxial anesthesia with ropivacaine is safe in malignant hyperthermia patients. Spinal clonidine can be safely added to LA in order to prolong the anesthetic block.

Key words: Malignant hyperthermia, spinal ropivacaine

Resumen

Informamos el caso de una paciente Mexicana susceptible a desarrollar hipertermia maligna que fue programada para aumento mamario y lipoescultura de abdomen. Se anestesió con una mezcla subaracnoidea de ropivacaína-clonidina hiperbárica. El bloqueo se extendió al dermatoma T2 y la cirugía transcurrió sin incidentes. No se usó dantroleno profiláctico y la enferma no tuvo datos clínicos ni de laboratorio de hipertermia maligna. Se concluye que los enfermos con antecedentes de hipertermia maligna se pueden anestesiar con ropivacaína neuroaxial.

Palabras clave: Hipertermia maligna, ropivacaína subaracnoidea

Malignant hyperthermia (MH) is a fulminant life-threatening, acute phamacogenetic disorder, developing during or after general anesthesia. Both a genetic predisposition and one or more triggering agents are necessary to evoke MH. Triggering agents include all volatile anesthetics (chloroform, ether, methoxifluorane, halothane, enflurane, isoflurane, sevorane, desflurane) and depolarizing muscle relaxant succinylcholine. Other drugs have been involved like d-tubocurarine and phenothiazines. All other anesthetics drugs including nitrous oxide, benzodiazepines, barbiturates, ketamine, etomidate, propofol, droperidol, opiates, anticholinergics, anticholinesterases, and non-depolarizing muscle relaxants are safe medications and can be used in MH patients. (1,2,3,4)
   Although there are few cases of MH linked to local anesthetics (LA),(5,6,7,8,9)  these drugs have been considered safe in those patients who are susceptible (MHS) to develop MH.(4,10-20) Harrison y Morrel (21)  infused intravenous lidocaine and bupivacaine yielding plasma concentration similar to those reported in humans during epidural analgesia and had a negative response in MHS swine. They concluded that lidocaine and bupivacaine are safe in those persons known to be genetically susceptible to MH.
   To our knowledge there are very few reported cases using neuroaxial ropivacaine in MHS patients. The first case was informed in Spain in 2002 using cervical epidural ropivacaine in a patient with family history of MH.(22) A second report was an USA patient with the King-Denborough syndrome, a rare disease associated with myopathy and susceptibility to MH. This patient received epidural ropivacaine.(23) The third case  was a Japanese MHS pregnant patient who also received epidural ropivacaine.(24) None of these patients developed signs of MH.
   We described a Mexican patient who has history of MH symptoms on her childhood, and was managed safely with a mixture of spinal ropivacaine-clonidine.
 

Case report

A 26 years old woman weighing 55.4 kg was scheduled for breast augmentation and abdominal liposuction. Her past medical history called our attention; a short but very crucial note from her previous anesthesiologist mentioned that when she was 11 years old, the patient developed an abnormal reaction to succinylcholine injection given to intubate her trachea during anesthesia for angiography. The reaction consisted of trismus, without evidence of other muscle contractions and postoperative myoglobinuria with elevated CPK. Her temperature rose one degree centigrade during the procedure. Several days after the patient underwent to a craniotomy in which no halothane, nor succinylcholine were used. Extensive monitoring revealed no evidence of hyperpyrexic reaction. Patient did well postoperatively. CPK was 1600 units postoperatively and declined over the next few days to near normal levels. Otherwise, she has had a normal life. After a consultation to her plastic surgeon for breast augmentation and liposculpture, the patient requested to be seen at our preanesthesia clinic in order to be evaluated and planned for the anesthesia technique. Although the patient was against regional anesthesia, we had a long discussion and convinced her to accept a combined epidural-spinal anesthesia technique. Rutinary blood test and CPK were normal. At her physical revision there were no abnormalities. One hour prior to anesthesia, she received 2 mg of sublingual lorazepam plus 0.1 mg oral clonidine. Continuous EKG, non invasive blood pressure, pulse oxymetry, and temperature monitors were attached to the patient before the block. With the patient in right lateral decubitus, L2-L3 interspace was identified and prepped with iodine, the skin injected with 2 mL of plain 0.75% ropivacaine, a 29 G spinal needle Quincke type point (Becton-Dickinson® ) was inserted. Once the subaracnhoid space was identified, and a droop of CSF was at the needle hub, a dose of 18.5 mg of hyperbaric 0.75% ropivacaine was slowly injected, followed by clonidine 75 µg. An epidural catheter was placed under local anesthesia with plain ropivacaine through an 18 G Tuohy needle inserted at L3-L4 space. The patient was positioned on her back and extreme Trendelemburg position was given until the sensitive spinal block reached T2, and then the patient was returned to a flat dorsal decubitus. Breasts implants were done first followed by abdominal and hips liposculpture. She needed no extradural injection of ropivacaine, and no incidents were developed during the anesthesia. Blood gases were normal and postoperative CPK was 45. Postoperative analgesia was managed with oral tramadol and ketorolac tromethamine ATC. She went home the next day.
 

Discussion

MH is an inherited dangerous illness characterized by a hyper metabolic state which is triggered when the person is exposed to certain anesthetic drugs. It is believed to be due to a reduction in the reuptake of calcium by the sarcoplasmic reticulum necessary for termination of muscle contraction. Sustained muscle contraction is followed by a hyper metabolic condition including tachycardia, hypercarbia, acidosis, glycolisis, hypoxemia, and heat production. MH occurs in 1 in every 15,000 pediatric anesthetics and 1 in every 50,000 adult anesthetics, with a mortality rate of about 10%. Anyone who is involved with anesthesia must have an up to date knowledge on its pathophysiology, prevention, diagnosis, and treatment of this potentially mortal entity.
   Anesthesia for patients with known MH susceptibility must be done only with non-triggering anesthetics. Evading all triggering agents is mandatory (see table 1) and several anesthesia methods needs to be discussed with the patient long before the surgery. We must consider total intravenous anesthesia, i.v. sedation, monitored anesthesia procedures, regional anesthesia, or general anesthesia using nitrous oxide-opioids and nondepolarizating muscle relaxants. The anesthesia machine must to be cleaned by changing the soda lime, removing all vaporizers, replacing the fresh gas hose, using a disposable circle and flushing the machine with 10 L/Min of air or oxygen for five minutes. We never know when the anesthesia machine needs to be used. All necessary equipment and drugs needed in the case of an MH attack must be available inside the operating room.

Table 1. Unsafe an safe drugs in MH patients

  • Unsafe drugs
    • Depolarizing muscle relaxants (succinylcholine)
    • Inhalational agents (cyclopropane, methoxifluorane, halothane, enflurane, isoflurane, sevoflurane, desflurane)
  • Insufficient data / controversial
    • d-Tubocurarine
    • Phenothiazines
  • Safe drugs
    • Antibiotics
    • Antihistamines
    • Antipyretics
    • Barbiturates (thiopental, methoexital)
    • Benzodiazepines (midazolan, diazepam, lorazepan)
    • Droperidol
    • Ketamine (inherent circulatory effects may mimic MH)
    • Local anesthetics (lidocaine, bupivacaine, ropivacaine)*
    • Nitrous oxide
    • Nondepolarizating muscle relaxants (pancuronion, rocuronium, vecuronium)
    • Opioids (morphine, meperidine, fentanyl, sufentanyl)
    • Propofol
    • Propranolol
    • Vasoactive drugs

* Some LA have been involved in MH. See text

   Although local and regional anesthesia are safe in most patients who are genetically predisposed to develop MH, it is recommendable to assume that few MHS patients will develop MH during or after the use of LA. There are several reports describing the use of esters and amino-amide LA for regional anesthesia or others non anesthesia scenarios triggering MH symptoms. Motegi et als.(5) described a MHS patient who developed signs of MH after using amides or ester type LA. Klimanek and coworkers (6) reported a 35 years old female patient who developed MH 30 minutes after epidural injection of 300 mg of lidocaine and 50 mg of bupivacaine. A patient with confirmed history of MH due to enflurane was managed with epidural procaine chloride and MH occurred. The authors attributed that tourniquet and stress were the provocative MH factors.(7) Vanek and Valenta (8) described another case of MH in conjunction with extradural anesthesia. Tatsukawa et als (9) described a 72 years old patient treated with i.v. lidocaine for ventricular arrhythmias who developed fever, generalized twitching, and lost of consciousness. Serum and urinary myoglobin were elevated. This case responded to dantrolene.
   Several researchers have been done studies in MH susceptible animals in order to determine the role of LA triggering MH. Harrison and Morrel (21) report a negative response in swine treated with i.v. infusion of lidocaine and bupivacaine reaching plasma concentration similar or exceed those reported during human peridural analgesia. Berkowitz and Rosenberg (25) used peripheral nerve blocks with 1% to 1.25% mepivacaine (8 mg/kg up to a limit of 400 mg) in patients undergoing muscle biopsy for the diagnosis of MH. Of the 11 cases with positive MH biopsies (caffeine-halothane contracture test) no one developed clinical evidence of MH reaction. The authors concluded that the combination of femoral with lateral femoral cutaneous nerve blocks with mepivacaine is a safe procedure in MHS patients.
   Ropivacaine, an amino-amide levoisomeric LA has been used safely in almost every regional anesthesia technique, even in the subaracnhoid space (26,27,28). Maemura (29) studied the ropivacaine effects on calcium (Ca) functions using the extensor digitorum longus muscle of male Hartley guinea pigs. He found that ropivacaine accelerated the Ca induced Ca release (CICR) rate at nonclinical concentrations, and suggested that this amide LA can be used safely in patients MHS. To our knowledge, there are only 3 cases of MHS patients managed with neuroaxial anesthesia with ropivacaine. Molina et als. (22) reported the first case in Spain; a 47 years old, female patient with history of two family deaths by MH while under general anesthesia. She was anesthetized twice with cervical epidural injection of 0.5% ropivacaine for breast surgery and postoperative analgesia using 0.2% ropivacaine. Habib et als. reported in the USA the second case; a female  patient with history of MH related to King-Denborough syndrome, a rare disorder that is associated with myopathy and susceptibility to MH. She was managed with extradural ropivacaine 0.08% plus fentanyl 2 μg/mL for labour patient controlled epidural analgesia. Matsuoka et als. (24) described a Japanese female patient with disposition for MH who was anesthetized several times with amino-amides LA (lidocaine, mepivacaine and ropivacaine) administered in the epidural cavity. These authors used 1.0% epidural ropivacaine for cesarean section. None of these patients developed signs of MH. Our patient is the first MHS patient managed with intratecal injection of ropivacaine, and the fourth treated with neuroaxial ropivacaine. The spinal injection of 18.5 mg of hyperbaric ropivacaine mixture with clonidine was safe and long enough to perform both surgeries.
 

Table 2. Management of MHS patients
  • Extensive preoperative anesthesia evaluation
  • Prepare anesthesia machine; remove all vaporizes, replace CO2 canisters, bellows, and gas hose.
  • Flush anesthesia machine for 30 minutes with oxygen 10 L/min.
  • Bring the MH cart inside the OR (this cart contains all supplies to resuscitate patients with MH)
  • Always scheduled your patient as the very first case of the day, and notify the post anesthesia care unit and the intensive care unit to be prepare to make available the necessary manpower
  • Consider dantrolene and sedation as premedicants
  •  Check CPK, ABG preoperatively, trans anesthesia and immediate postoperative period.
  • Discuss your patient with a college and always work with a partner in the OR
  • Always consider several anesthetic possibilities; regional anesthesia, local anesthesia, plexus anesthesia, monitored anesthesia care, sedative techniques. If general anesthesia is used avoid known triggering drugs.
  • After surgery continue to monitor laboratory values. Keep your patient properly monitored in a safety environment. Keep them as inpatients at least for one day.
  • Advice the OR, recovery room an intensive case personal of your MHS patient

Management of MHS patients is based of prophylactic measures.(Table 2) When the anesthesiologist is aware of the problem, as we were with our case, there is no need to risk the patient life. If regional anesthesia is possible, it should be considered as the technique of choice; neuroaxial procedures (extradural, subarachnoid, or mixed spinal-epidural), plexus anesthesia, or LA infiltration. Historical reports on MH warned against the use of amide LA in persons susceptible to the syndrome. The predominance of data supports the safety of both ester and amide LA in such patients, and these drugs should not be withheld from persons at risk for developing MH, but it must keep in mind the remote possibility that LA agents may trigger this deadly syndrome. There is no agreement if it is necessary to use prophylactic dantrolene in MHS planed under regional anesthesia procedures. Abballe et als (30) published a case of a woman susceptible to develop MH, she received oral prophylactic dantrolene before spinal bupivacaine and developed no signs of MH. Others reports mention oral or intravenous prophylaxis  with dantrolene before regional. anesthesia.(16,20,31)
If general anesthesia needs to be used, follow the steps listed in table 2. Some susceptible patients may develop MH despite multiple prior uneventful exposures to known triggering drugs. Some other drugs have been found to be safe in patients susceptible to MH.(Table 1)
   Due to extraordinary risk of complications or even death in MHS patients, most plastic surgeons may hesitate to perform surgery on these patients. Our case is in agreement with Wackym and cols opinion (32) that plastic surgery can be performed safely when anesthesia is properly selected; general or regional techniques can be safely used.
   Finally, in the event of MH crisis, it is useful to know that in Northwestern Mexico there is a hotline were anybody can call searching for assistance and even for the first dose of dantroleno (01-664-684-89-05 or 01-664-684-89-06). You can also get help asking the Comité de hipertermia maligna of the Federación Mexicana de Anestesiología, A.C. accessing www.fma.org.mx . In inland Mexico you may find information calling the Hospital Infantil de México, Anesthesia Department at 01(55)-52-28-99-17. They have special interest and experience with MH patients.
   In conclusion, we described a MH predisposed women who was safely managed with spinal ropivacaine-clonidine. She developedd no signs of MH. Therefore, LA agents should not be withheld from MHS patients, although either prophylactic measures and or MH rescue team needs to be available. 

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