Gobierno de la Provincia de Crdoba Ministerio de Salud Hospital de Nios de la Santsima Trinidad Comit de Farmacoteraputica

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Datos del Solicitante Solicitante: UTI rea: Servicio de Enfermera Tema de la consulta Uso prolongado de diazepam en ttanos Respuesta Esta consulta se deriv al CIME, por lo que se agradece especialmente a la Facultad de Ciencias Qumicas de la Universidad Nacional de Crdoba, y a su excelente equipo de profesionales. En este caso a las farmacuticas Mariana Cafaratti y Liliana Bessone, que elaboraron el presente informe que aqu se transcribe: DIAZEPAM
Gold Standard/Elsevier Clinical Pharmacology [en lnea]. EEUU (Acceso restringido). Acceso: 3/05/12 Disponible en

Consulta N: 16 Fecha: 04/05/2012

http://www.clinicalpharmacology.com Indications/Dosage For the treatment of muscle spasm due to local pathology such as muscle or joint inflammation or trauma; athetosis; stiff-man syndrome; tetanus; or spasticity due to upper motor neuron diseases such as cerebral palsy: Oral dosage (oral solution or regular tablets): Adults: 210 mg PO three to four times per day. Geriatric: 22.5 mg PO one to two times per day, increasing the dose according to response and patient tolerability. Infants >= 6 months, Children, and Adolescents: Initially, 12.5 mg PO three to four times per day. The dose may be increased as needed and tolerated.[28712] Neonates and Infants < 6 months: Safety and efficacy have not been established. Intravenous and Intramuscular dosage: Adults : 510 mg IM or IV initially, repeated every 34 hours as needed. For tetanus, larger doses may be required. Children >= 5 years and Adolescents: 510 mg IM or IV every 34 hours as needed.[43931] Infants and Children < 5 years: 12 mg IM or IV every 34 hours as needed.[43931] Neonates: Safety and efficacy have not been established.

DIAZEPAM
Ministerio de Sanidad y Consumo. Informacin de Medicamentos para el Profesional Sanitario. USP-DI. 2da Edicin Espaola. Madrid. Espaa. 1995

Hospital de Nios de la Santsima Trinidad - Comit de Farmacoteraputica TE: 0351-4586400 int. 606 - email: farmacoteraputica@hospitaldeninos.com.ar

Gobierno de la Provincia de Crdoba Ministerio de Salud Hospital de Nios de la Santsima Trinidad Comit de Farmacoteraputica

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Dosis peditrica habitual Coadyuvantes de relajantes del msculo esqueltico: Ttanos: Nios de 5 aos en adelante: IM o IV, de 5 a 10 mg cada 3 4 hs, la dosificacin puede repetirse cada 3 o 4 horas segn las necesidades.

DIAZEPAM
American Society of Health-System Pharmacists (ASHP) AHFS DI Monographs (on-line) EEUU Acceso: 3/05/12 Disponible en:

http://www.drugs.com/monograph/ Dosage Pediatric Patients Tetanus IV or IM Children >30 days to 5 years of age: 12 mg. May repeat dose every 34 hours as needed. Children >5 years of age: 510 mg. May repeat dose every 34 hours as needed. Prescribing Limits Pediatric Patients IV Maximum 0.25 mg/kg as a single initial dose, repeated at 15- to 30-minute intervals to a maximum total dose of 0.75 mg/kg _______________________________________________________________________________________
Sean C Sweetman, editor. The Complete Drug Reference. Martindale. 36th Edition. London-Chicago Pharmaceutical Press. 2009

Muscle spasm. Diazepam and other benzodiazepines may be used for the relief of muscle spasm (p.1887) of various aetiologies including that secondary to muscle or joint inflammation or trauma, such as in acute low back pain (p.7), or resulting from spasticity (p.1887), dystonias (p.809), stiff-man syndrome (see below), cerebral palsy, poisoning, or tetanus (p.1901). High doses are often required and treatment may be limited by adverse effects or by risk of dependence. _______________________________________________________________________________________ NEONATAL TETANUS TREATED WITH HIGH DOSAGE DIAZEPAM B. H. KHOO, E. L. LEE, K. L. LAM. Neonatal tetanus treated with high dosage diazepam Archives of Disease in Childhood, 1978, 53, 737-739

Hospital de Nios de la Santsima Trinidad - Comit de Farmacoteraputica TE: 0351-4586400 int. 606 - email: farmacoteraputica@hospitaldeninos.com.ar

Gobierno de la Provincia de Crdoba Ministerio de Salud Hospital de Nios de la Santsima Trinidad Comit de Farmacoteraputica

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Sedation. Muscle relaxation and sedation were achieved by continuous IV infusion of high dose diazepam (20-40 mg/kg per day) and intragastric phenobarbitone (10-15 mg/kg per day in 4 divided doses). The initial total daily maintenance dose of diazepam was 20 mg/kg and this could be increased gradually to a maximum of 40 mg/kg until spasms were controlled. Additional bolus injections of diazepam (5-10 mg) were administered if spasms were severe and frequent; but these were not given more than 4 times in 24 hours. Once spontaneous spasms had ceased for at least 48 hours, the dose of diazepam was reduced every third day by approximately 10% of the previous dose. If dosage reduction was attempted too rapidly, spontaneous spasms recurred and subsequent control was sometimes difficult. Diazepam was given via the nasogastric tube when the spasms were controlled and nasogastric feeding had been established; this was usually achieved after 5 to 10 days of intravenous therapy. A few patients had hiccups but these were effectively controlled by 2 to 5 mg IV chlorpromazine. Discussion The main side effects encountered with this regimen were severe drowsiness, coma, and occasionally apnoeic episodes which were reversible when the dose of the drug was reduced. These patients tended to have excessive pooling of secretions in the oropharynx because the swallowing reflex was depressed, and they required frequent suction. Respiratory arrest is another potential hazard, but the continuous infusion of diazepam did not seriously depress respiration. Renal, hepatic, and haematological functions were also unaffected. Although diazepam forms a white precipitate when diluted with dextrose saline solutions, this does not result in any adverse reaction nor does it reduce the therapeutic potency (Smith and Masotti, 1971). However, the solvent of diazepam contains 5 % sodium benzoate which competes with bilirubin for the binding sites in albumin, thus increasing the risks of hyperbilirubinaemia (Schiff et al., 1971). Hyperbilirubinaemia was not a problem as most of our patients were term infants and more than 7 days old at admission. In this series only 3 developed neonatal jaundice; the maximum total bilirubin levels reached were 8*5, 10*8, and (Case 15) 18*2 mg/ 100 ml respectively. Case 15 was treated with phototherapy and serum bilirubin fell to 10*8 mg/ 100 ml 4 days later; unfortunately this patient was lost to follow-up. During intravenous diazepam treatment, care was taken to ensure that the percutaneous intravenous needle was not dislodged as skin necrosis can result from subcutaneous perfusion of the drug.

LISTA DE TODAS LAS REFERENCIAS CONSULTADAS

1. Okoromah CN, Lesi FEA. Diazepam para el tratamiento del ttanos (Revisin Cochrane traducida). En: La Biblioteca Cochrane Plus, 2008 Nmero 4. Oxford: Update Software Ltd. Disponible en: http://www.update-software.com. (Traducida de The Cochrane Library, 2008 Issue 3. Chichester, UK: John Wiley & Sons, Ltd.)

2. B. H. KHOO, E. L. LEE, K. L. LAM. Neonatal tetanus treated with high dosage diazepam. Archives of Disease in Childhood, 1978, 53, 737-739
3. 4. Sean C Sweetman, editor. The Complete Drug Reference. Martindale. 36th Edition. London-Chicago Pharmaceutical Press. 2009 American Society of Health-System Pharmacists (ASHP) AHFS DI Monographs (on-line) EEUU Acceso: 3/05/12 Disponible en:

http://www.drugs.com/monograph/
Hospital de Nios de la Santsima Trinidad - Comit de Farmacoteraputica TE: 0351-4586400 int. 606 - email: farmacoteraputica@hospitaldeninos.com.ar

Gobierno de la Provincia de Crdoba Ministerio de Salud Hospital de Nios de la Santsima Trinidad Comit de Farmacoteraputica
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Ministerio de Sanidad y Consumo. Informacin de Medicamentos para el Profesional Sanitario. USP-DI. 2da Edicin Espaola. Madrid. Espaa. 1995

6.

Gold

Standard/Elsevier

Clinical

Pharmacology

[en

lnea].

EEUU

(Acceso

restringido).

Acceso:

3/05/12

Disponible

en

http://www.clinicalpharmacology.com

Para ampliar la informacin, pueden consultar la excelente Revisin Cochrane: Diazepam para el tratamiento del ttanos
Okoromah CN, Lesi FEA. Diazepam para el tratamiento del ttanos (Revisin Cochrane traducida). En: La Biblioteca Cochrane Plus, 2008 Nmero 4. Oxford: Update Software Ltd. Disponible en: http://www.updatesoftware.com. (Traducida de The Cochrane Library, 2008 Issue 3. Chichester, UK: John Wiley & Sons, Ltd.) Para cualquier consulta o inquietud, dirigirse al Area de Produccin Cientfica. Int. 606.

farmacoterapeutica@hospitaldeninos.com.ar aledeguernica@yahoo.com.ar. Alejandra de Guernica.

Hospital de Nios de la Santsima Trinidad - Comit de Farmacoteraputica TE: 0351-4586400 int. 606 - email: farmacoteraputica@hospitaldeninos.com.ar