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Dantrolene

Dantrolene sodium is a muscle relaxant that is currently the only specific and effective treatment for malignant hyperthermia. It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegia, cerebral palsy, or patients with multiple sclerosis) and ecstasy intoxication. more...

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Chemistry

Chemically it is a hydantoin derivative, but does not exhibit antiepileptic activity like other hydantoin derivates such as phenytoin.

The related substance azumolene is under development for similar indications. It has a bromine residue instead of the nitrite group, and is 30 times more water-soluble.

Mode of action

Dantrolene depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor, and decreasing intracellular calcium concentration.

Contraindications

  • preexisting liver disease
  • compromised lung function
  • severe cardiovascular impairment
  • known hypersensitivity to dantrolene
  • pediatric patients under 5 years of age
  • whenever good muscular balance/strength is needed to maintain an upright position, motoric function, or proper neuromuscular balance

If the indication is a medical emergency such as malignant hyperthermia, the only significant contraindication is hypersensitivity.

Pregnancy and Lactation

  • Pregnancy: Adequate human studies are lacking, therefore the drug should be given in pregnant women only if clearly indicated.
  • Lactation: Dantrolene should not be given to breastfeeding mothers. If a treatment is necessary, breastfeeding should be terminated.

Side-effects

CNS side effects are quite frequently noted and encompass speech and visual disturbances, mental depression and confusion, hallucinations, headache, insomnia and exacerbation or precipitation of seizures, and increased nervousness. Infrequent cases of respiratory depression or a feeling of suffocation have been observed. Dantrolene often causes sedation severe enough to incapacitate the patient to drive or operate machinery.

Gastrointestinal effects include bad taste, anorexia, nausea, vomiting, abdominal cramps, and diarrhea.

Hepatic side effects may be seen either as asymptomatic elevation of liver enzymes and/or bilirubin or, most severe, as fatal and nonfatal hepatitis. The risk of hepatitis is associated with the duration of treatment and the daily dose. In patients treated for hyperthermia, no liver toxicity has been observed so far.

Pleural effusion with pericarditis (oral treatment only), rare cases of bone marrow damage, diffuse myalgias, backache, dermatologic reactions, transient cardiovascular reactions, and crystalluria have additionally been seen. Muscle weakness may persist for several days following treatment.

Mutagenicity and Carcinogenity

Dantrolene gave positive results in animal high dose studies (with and without enzymatic activation) regarding mutagenicity and carcinogenity. No evidence for human mutagenicity and carcinogenity has been found during the long years of clinical experience.

Read more at Wikipedia.org


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What is 'general anesthesia'?
From Cosmetic Surgery Times, 4/1/05 by Barry L. Friedberg

Regarding Dr. Wheeland's editorial ("Office-based cosmetic surgery: How can it be proven safe?" Cosmetic Surgery Times Jan/Feb p.3), I am inclined to support Dr. Wheeland's conclusion that general anesthesia (GA) should probably be restricted from use in the office-based practice of cosmetic surgery. My concern is with the undefined use of the term 'general anesthesia'--which may have some unforeseen consequences inimical to patient safety in the office-based setting for cosmetic surgery.

GA can be using inhalational agents like isoflurane, desflurane and sevoflurane. GA is a state defined by bispectral index (BIS) values

from 40 to 60 on a 100-point scale. GA is relatively contraindicated in cosmetic surgery because of the small but unnecessary risk of malignant hyperthermia. Intravenous (IV) approaches can simulate the conditions of GA. GA provides conditions that permit patients to have surgery without hearing, feeling or remembering the experience. One suitable IV alternative with an outstanding record of safety is my propofol ketamine (PK) monitored anesthesia care (MAC).

From March 26, 1992 through January 27, 2005, more than 3,000 patients have successfully received PK MAC without a single death. All current cosmetic procedures were successfully managed. No patients were admitted to the hospital for PONV or postoperative pain management. PK MAC preserves the normal muscle pump of the legs. PK MAC patients receive preemptive analgesia and ambulate rapidly even after abdominoplasty surgery. There have been no cases of thromboembolic phenomena in any of my 3,000 patients.

Since December 26, 1997, I have routinely monitored my patients with the BIS brain monitor. My patients have their propofol titrated between 60 and 75. This level of sedation is either moderate or deep sedation depending on whether passive or active airway intervention is required to maintain the airway. Clearly PK MAC sedation at BIS 60 to 75 is not GA at BIS 40 to 60! Patients receive the 'illusion' of GA (BIS 40 to 60) with the lesser trespass of sedation (BIS 60 to 75). BIS-monitored PK MAC is now called the minimally invasive anesthesia (MIA)[TM] technique.

In every state except Florida, PK MAC is recognized as IV sedation.

The Medical Board of Florida has arbitrarily classified PK MAC as GA.

The practical meaning of the ruling is to require every office-based surgery suite in Florida desiring to have the benefits of PK MAC to be required to increase their classification from a 'B' to a 'C' facility. 'C' facilities must have 1) an anesthesia machine, 2) scavenging, 3) dantrolene. PK MAC is a non-triggering IV technique. Florida's requirements add substantial costs without adding a scintilla of patient safety. Furthermore, the Medical Board of Florida has rejected numerous e-mail and phone requests to list the classification of PK MAC as GA as an item on the agenda for discussion.

One might reasonably ask why I, as a California anesthesiologist, should be concerned about what the Florida Medical Board has classified as GA. When Florida enacted a 4,000 cc limit on office-based liposuction, California followed quickly with a 5,000 cc limit. Florida enacted mandatory reporting of all office-based deaths in addition to an eight-hour limit on office-based cosmetic surgery. I support the liposuction limit, mandatory reporting, as well as the eight-hour limit. However, classifying PK MAC as GA has no basis in medical fact and does nothing to increase patient safety. Unreasonable action by the Florida Medical Board may some day come to haunt my professional life in California.

Thank you for the opportunity to express my concerns about this vital topic.

Barry L. Friedberg, M.D.

clinical instructor in anesthesia, University of Southern California

www.doctorfriedberg.com

COPYRIGHT 2005 Advanstar Communications, Inc.
COPYRIGHT 2005 Gale Group

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