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Neuroleptic malignant syndrome in a burn patient
ELSEVIER
Burns
24 (1998)
573-575
Neuroleptic malignant syndrome in a burn patien Joseph Still *, Bruce Friedman, Edward Law, Scott Deppe, Neil Epperiy, Hermann Orlet Columbia-Augusta
Medical
Center,
1220 George
C, Wilson
Dr.,
Augusta>
GA 30914-3726,
USA
Accepted9 March 1998
Abstract A 39 year laid white male with a 55% total body surface burn who developed neuroleptic malignant syndrome (NMS) during his acute corr:se is reported. The patient had several acute sinusitis and septic episodes during his acute course. On postburn day 31, he developed a temperature of 108.4OF(42.4’C). This responded promptly to Dantrolene and Bromocriptene. His recovery was uneventful. NMS is a drug-related response to various medications, such as Haloperidol, which the patient was receiving. NMS must be considered as part of the differential diagnosis of fever in burn patients receiving medication known to cause the syndrome. 0 1998 Elsevier Science Ltd for ISBI. All rights reserved. Keywords:
Neurolepticmalignant syndrome;Hyperthermia;Infection
during an industrial accident at a nuclear power plant. Triage occurred at the referring institution where he was intubated. Resuscitation was begun followed by air evacuation to the Burn Unit. Review of systems and past history were unremarkable. Pertinent physical findings included a 55% total body surface burn involving the head, face, neck, upper arms and hands and scattered areas on the anterior and posterior trunk. The burns were blistered and moist and initially appeared to be entirely second degree. Inspiratory wheezes were present and respiratory tract damage was confirmed by bronchoscopy; mechanical ventilation continued. Resuscitation using Ringer’s lactate was carried out uneventfully. The patient was taken to the operating room on post-burn day (PBD) 1 and underwent debridement of the head, face, neck, arms, back and legs with application of porcine xenografts. Early tracheostomy was performed anticipating prolonged mechanical ventilator support due to severe inhalation injury. The puhnonary status deteriorated, infiltrates developed over the next few days and pneumonia was diagnosed bronchoscopically. Antibiotics were selected
I. Introduction Neuroleptic malignant syndrome (NMS) is an occasionally encountered, life threatening complication of drug therapy. lt usually develops in response to administration of certain drugs, such as butyrophenones (Haloperidol). phenothiazines and thioxanthenes. Predisposing factors include exhaustion and dehydration. Hyperthermia, hyperrigidity, altered mental status and autonomic instability are key manifestations. We report a severely burned patient in whom this problem was encountered. The patient responded well to therapy.
2. Case report This was the first time admission to the Burn Unit at Columbia-Augusta Medical Center of a 39 year old white male who was injured by superheated steam
* correspondingauthor. 0305.4i79/98/$i9.00 :Q 1998ElsevierScience PII:
SO305-4179(98)00056-4
Ltd
for ISBI.
All rights
reserved.
514
J. Still et al. 1 Bums
based on subsequent bronchoalveolar lavage culture results. A dual-lumen enteral feeding tube was placed. Renal parameters remained normal and mechanical ventilation continued. Anemia secondary to blood loss several transfusions. A developed, necessitating bronchoscopy on post burn day (PBD) 13 revealed improvement. An episode of methicillin resistent, StaphJdococcus ~~z~~ez~s bacteremia developed on PBD 16 requiring intravenous Vancomycin. The temperature was initially 1011102°F (38.3-38.9C) but returned to normal after several days. On PBD 22, burn debridement and patchy areas of split thickness skin grafting were performed without complications. Simultaneously, the pulmonary function improved and a weaning protocol was initiated. During this period, Haloperidol along with benzodiazepines were used to control agitation and delerium. Consistent hyperthermia was observed in the lOl;04’F (38.3-40’(Z) range. Fever work-up was initiated ruling out central line infection. Sinusitis was suspected on a clinical basis and confirmed by CT scan. A blood culture drawn on PBD 25 showed Can&da parapsilosis and amphotericin B was begun on PBD 29. On PBD 31. rapidly progressive fever (unresponsive to antipyretics) rose beyond 104OF (4O’Q peaking at 108.4OF (42.4’C). A single dose of IV Dantrolene was given and Bromocriptine was started nasogastrically at 2.5 mg q 8 h. The patient’s temperature decreased to 1Ol’F (38.3C) within 90 min and subsequently> remained stable over the next several days. On PBD 32, bilateral maxillary sinus irrigation was carried out by the otolaryngology staff. Cultures revealed Proteus mimbilis and microaerophilic Streptococci; antibiotics were adjusted. On admission, the creatinine kinase (CK) was over 1000, rapidly falling to normal. On PBD 3 1, coinciding with the acute hyperthermia, the CK rose again to over 1000, returning to normal within 2 days after administration of Dantrolene and Bromocriptine. An Aldolase level obtained at this time was 28 (normal 0.0-8.2 pl). Subsequently, the burn wound healed completely. Decannulation occurred and Bromocriptine was discontinued on PBD 40. The patient was discharged to a rehabilitation facility on PBD 41.
3. Discussion NMS is a rare and potentially lethal complication of treatment with neuroleptic drugs and other agents of similar Ichemical structure. Prager et al. [I] report an occurrence ra.te of 0.07 to 2.2Oh in patients receiving such medication. NMS is also encountered in some
24 (1998)
573-575
medical conditions including Parkinson’s disease. The mortality rate has been reported as high as 25Oh. NMS was originally reported by Delay and Dinger [l]. As described by other authors [2,3], the pathophysiology of NMS, involves increased heat production in muscle sarcoplasmic reflux, mediated by the interruption of central thermoregulatory pathways. Neuroleptic drugs induce a blockade of dopaminergic receptors in the hypothalamus dysregulating central temperature control. NMS may be precipitated by blockade of central dopamine receptors, Dl and D2? in the hypothalmus and basal ganglia. This premise is supported by the fact that pharmacologic reductions in Levodopa may precipitate NMS. Interference with central Dopamine action at the level of hypothalamus may lead to disorders in thermal regulation. Interference with the basal ganglia then results in skeletal muscle hypertonicity> prolonged muscle contractions and further heat production. Dantrolene is effective in the treatment of malignant hyperthermia, heat stroke and NMS by affecting muscle contraction preventing the calcium dependent contraction of actin and myosin in muscle allowing temperature to fall. This is the postulated mechanism of control of hyperthermia. Bromocriptine acts in a similar fashion. Prager [l] and Lavie [4] stress the difficulty of diagnosing NMS. Symptoms and signs include hyperthermia, autonomic dysfunction pyramidal signs, rigidity and neurologic deficits. Tachycardia, tachypnea, diaphoresis, hypotension, leukocytosis and liver function abnormalities may also be present. Shalev [2] found that the time of onset of symptoms varied from 45 min to 65 days after administration of a new phenothiazine. CK was correlated to the intensity of NMS and its linear decline reflected symptoma tic improvement. Drugs known to precipitate NMS include chlorpromazine, metoclopramide and Haloperidol, others. The condition must be differentiated from central nervous system disorders, such as head trauma, meningitis and status epilepticus and from systemic disorders, such as hyperthyroidism, malignant hyperthermia, heat stroke and sepsis. Treatment should include discontinuing dopamine antagonists, supportive care such as hemodynamic support, correction of any volume related problems, aggressive cooling measures (cooling blankets, etc.) and provision of ventilatory and respiratory support as necessary. Dantrolene, Bromocriptine and Amantadine are the pharmacologic agents of choice [2]. Therapeutic doses of these medications should be tried when acute exceptionally high fever I(> 105O) occurs in a clinical setting not consistent with a specific disease state.
J. Still et al. /Bum
Our patient’s burn wounds were essentially healed at the onset of the 108.4’ fever spike. Intravenous Haloperidol had been given within 48 h of the acute event and pansinusitis was concurrently diagnosed and treated. Treatment was underway with Amphotericin B for CamiWa parapsilosis fungemia. In spite of other potential sources of fever, the dramatic response to one dose of IV Dantrolene was diagnostic for NMS. This was supported by the acute phase elevations of aldoIase and CK, which returned to normal within 48 h and the clinical improvement during the same time frame. In conclusion? in reviewing the literature, this appears to be the first case reported of NMS in the critically ill burn. NMS represents a possible cause of
24 fl998)
573-575
il5
very high fever in burn patients receiving drugs likely ~toprecipitate the syndrome.
References [l]
Prager L, Millham Stern T. Neuroleptic malignant syndrome: a review for intensivists. J Intensive Care Med 1994:9:227-34. [2] Shalev A, Munitz H. The neuroleptic malignant syndrome: agent and host interaction. Acta Psych Stand 1986;73:337-47. [3] Bismuth C, Rohan-Chabot Pq Goulon M et al. Dantrolene: a new therapeutic approach to the neuroleptic malignant syndrome. Acta Neurol Stand 1984;70 (SuppI. 100):193-8. [4] Lavie C, Olmsted T, Ventura H et al. Neuroleptic malignant syndrome: an undiagnosed reaction to neuroleptic agents? PostGraduate Med 1986;80:171-178.
Burns
24 (1998)
573-575
Neuroleptic malignant syndrome in a burn patien Joseph Still *, Bruce Friedman, Edward Law, Scott Deppe, Neil Epperiy, Hermann Orlet Columbia-Augusta
Medical
Center,
1220 George
C, Wilson
Dr.,
Augusta>
GA 30914-3726,
USA
Accepted9 March 1998
Abstract A 39 year laid white male with a 55% total body surface burn who developed neuroleptic malignant syndrome (NMS) during his acute corr:se is reported. The patient had several acute sinusitis and septic episodes during his acute course. On postburn day 31, he developed a temperature of 108.4OF(42.4’C). This responded promptly to Dantrolene and Bromocriptene. His recovery was uneventful. NMS is a drug-related response to various medications, such as Haloperidol, which the patient was receiving. NMS must be considered as part of the differential diagnosis of fever in burn patients receiving medication known to cause the syndrome. 0 1998 Elsevier Science Ltd for ISBI. All rights reserved. Keywords:
Neurolepticmalignant syndrome;Hyperthermia;Infection
during an industrial accident at a nuclear power plant. Triage occurred at the referring institution where he was intubated. Resuscitation was begun followed by air evacuation to the Burn Unit. Review of systems and past history were unremarkable. Pertinent physical findings included a 55% total body surface burn involving the head, face, neck, upper arms and hands and scattered areas on the anterior and posterior trunk. The burns were blistered and moist and initially appeared to be entirely second degree. Inspiratory wheezes were present and respiratory tract damage was confirmed by bronchoscopy; mechanical ventilation continued. Resuscitation using Ringer’s lactate was carried out uneventfully. The patient was taken to the operating room on post-burn day (PBD) 1 and underwent debridement of the head, face, neck, arms, back and legs with application of porcine xenografts. Early tracheostomy was performed anticipating prolonged mechanical ventilator support due to severe inhalation injury. The puhnonary status deteriorated, infiltrates developed over the next few days and pneumonia was diagnosed bronchoscopically. Antibiotics were selected
I. Introduction Neuroleptic malignant syndrome (NMS) is an occasionally encountered, life threatening complication of drug therapy. lt usually develops in response to administration of certain drugs, such as butyrophenones (Haloperidol). phenothiazines and thioxanthenes. Predisposing factors include exhaustion and dehydration. Hyperthermia, hyperrigidity, altered mental status and autonomic instability are key manifestations. We report a severely burned patient in whom this problem was encountered. The patient responded well to therapy.
2. Case report This was the first time admission to the Burn Unit at Columbia-Augusta Medical Center of a 39 year old white male who was injured by superheated steam
* correspondingauthor. 0305.4i79/98/$i9.00 :Q 1998ElsevierScience PII:
SO305-4179(98)00056-4
Ltd
for ISBI.
All rights
reserved.
514
J. Still et al. 1 Bums
based on subsequent bronchoalveolar lavage culture results. A dual-lumen enteral feeding tube was placed. Renal parameters remained normal and mechanical ventilation continued. Anemia secondary to blood loss several transfusions. A developed, necessitating bronchoscopy on post burn day (PBD) 13 revealed improvement. An episode of methicillin resistent, StaphJdococcus ~~z~~ez~s bacteremia developed on PBD 16 requiring intravenous Vancomycin. The temperature was initially 1011102°F (38.3-38.9C) but returned to normal after several days. On PBD 22, burn debridement and patchy areas of split thickness skin grafting were performed without complications. Simultaneously, the pulmonary function improved and a weaning protocol was initiated. During this period, Haloperidol along with benzodiazepines were used to control agitation and delerium. Consistent hyperthermia was observed in the lOl;04’F (38.3-40’(Z) range. Fever work-up was initiated ruling out central line infection. Sinusitis was suspected on a clinical basis and confirmed by CT scan. A blood culture drawn on PBD 25 showed Can&da parapsilosis and amphotericin B was begun on PBD 29. On PBD 31. rapidly progressive fever (unresponsive to antipyretics) rose beyond 104OF (4O’Q peaking at 108.4OF (42.4’C). A single dose of IV Dantrolene was given and Bromocriptine was started nasogastrically at 2.5 mg q 8 h. The patient’s temperature decreased to 1Ol’F (38.3C) within 90 min and subsequently> remained stable over the next several days. On PBD 32, bilateral maxillary sinus irrigation was carried out by the otolaryngology staff. Cultures revealed Proteus mimbilis and microaerophilic Streptococci; antibiotics were adjusted. On admission, the creatinine kinase (CK) was over 1000, rapidly falling to normal. On PBD 3 1, coinciding with the acute hyperthermia, the CK rose again to over 1000, returning to normal within 2 days after administration of Dantrolene and Bromocriptine. An Aldolase level obtained at this time was 28 (normal 0.0-8.2 pl). Subsequently, the burn wound healed completely. Decannulation occurred and Bromocriptine was discontinued on PBD 40. The patient was discharged to a rehabilitation facility on PBD 41.
3. Discussion NMS is a rare and potentially lethal complication of treatment with neuroleptic drugs and other agents of similar Ichemical structure. Prager et al. [I] report an occurrence ra.te of 0.07 to 2.2Oh in patients receiving such medication. NMS is also encountered in some
24 (1998)
573-575
medical conditions including Parkinson’s disease. The mortality rate has been reported as high as 25Oh. NMS was originally reported by Delay and Dinger [l]. As described by other authors [2,3], the pathophysiology of NMS, involves increased heat production in muscle sarcoplasmic reflux, mediated by the interruption of central thermoregulatory pathways. Neuroleptic drugs induce a blockade of dopaminergic receptors in the hypothalamus dysregulating central temperature control. NMS may be precipitated by blockade of central dopamine receptors, Dl and D2? in the hypothalmus and basal ganglia. This premise is supported by the fact that pharmacologic reductions in Levodopa may precipitate NMS. Interference with central Dopamine action at the level of hypothalamus may lead to disorders in thermal regulation. Interference with the basal ganglia then results in skeletal muscle hypertonicity> prolonged muscle contractions and further heat production. Dantrolene is effective in the treatment of malignant hyperthermia, heat stroke and NMS by affecting muscle contraction preventing the calcium dependent contraction of actin and myosin in muscle allowing temperature to fall. This is the postulated mechanism of control of hyperthermia. Bromocriptine acts in a similar fashion. Prager [l] and Lavie [4] stress the difficulty of diagnosing NMS. Symptoms and signs include hyperthermia, autonomic dysfunction pyramidal signs, rigidity and neurologic deficits. Tachycardia, tachypnea, diaphoresis, hypotension, leukocytosis and liver function abnormalities may also be present. Shalev [2] found that the time of onset of symptoms varied from 45 min to 65 days after administration of a new phenothiazine. CK was correlated to the intensity of NMS and its linear decline reflected symptoma tic improvement. Drugs known to precipitate NMS include chlorpromazine, metoclopramide and Haloperidol, others. The condition must be differentiated from central nervous system disorders, such as head trauma, meningitis and status epilepticus and from systemic disorders, such as hyperthyroidism, malignant hyperthermia, heat stroke and sepsis. Treatment should include discontinuing dopamine antagonists, supportive care such as hemodynamic support, correction of any volume related problems, aggressive cooling measures (cooling blankets, etc.) and provision of ventilatory and respiratory support as necessary. Dantrolene, Bromocriptine and Amantadine are the pharmacologic agents of choice [2]. Therapeutic doses of these medications should be tried when acute exceptionally high fever I(> 105O) occurs in a clinical setting not consistent with a specific disease state.
J. Still et al. /Bum
Our patient’s burn wounds were essentially healed at the onset of the 108.4’ fever spike. Intravenous Haloperidol had been given within 48 h of the acute event and pansinusitis was concurrently diagnosed and treated. Treatment was underway with Amphotericin B for CamiWa parapsilosis fungemia. In spite of other potential sources of fever, the dramatic response to one dose of IV Dantrolene was diagnostic for NMS. This was supported by the acute phase elevations of aldoIase and CK, which returned to normal within 48 h and the clinical improvement during the same time frame. In conclusion? in reviewing the literature, this appears to be the first case reported of NMS in the critically ill burn. NMS represents a possible cause of
24 fl998)
573-575
il5
very high fever in burn patients receiving drugs likely ~toprecipitate the syndrome.
References [l]
Prager L, Millham Stern T. Neuroleptic malignant syndrome: a review for intensivists. J Intensive Care Med 1994:9:227-34. [2] Shalev A, Munitz H. The neuroleptic malignant syndrome: agent and host interaction. Acta Psych Stand 1986;73:337-47. [3] Bismuth C, Rohan-Chabot Pq Goulon M et al. Dantrolene: a new therapeutic approach to the neuroleptic malignant syndrome. Acta Neurol Stand 1984;70 (SuppI. 100):193-8. [4] Lavie C, Olmsted T, Ventura H et al. Neuroleptic malignant syndrome: an undiagnosed reaction to neuroleptic agents? PostGraduate Med 1986;80:171-178.