Diazepam for treating tetanus
Editorial Group: Cochrane Neonatal Group
Published Online: 26 JAN 2004
Assessed as up-to-date: 29 JUN 2004
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Okoromah CAN, Lesi AFE. Diazepam for treating tetanus. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD003954. DOI: 10.1002/14651858.CD003954.pub2.
- Publication Status: Edited (no change to conclusions)
- Published Online: 26 JAN 2004
Clinical management of the muscle spasms and rigidity of tetanus poses a difficult therapeutic problem to physicians everywhere, especially in resource poor countries. There are wide variations in therapeutic regimens commonly used in clinical practice due to uncertainties about effectiveness of conventional drugs. Diazepam compared to other drugs (eg phenobarbitone and chlorpromazine) may have advantages because of combined anticonvulsant, muscle relaxant, sedative and anxiolytic effects.
To compare diazepam to other drugs in treating the muscle spasms and rigidity of tetanus in children and adults.
We searched the Cochrane Neonatal Group trials register (June 2004), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to June 2004), EMBASE (1980 to June 2004), LILACS (2004), CINAHL (June 2004), Science Citation Index, African Index Medicus, conference abstracts and reference lists of articles. We contacted researchers, experts and organizations working in the field and used personal communication.
Randomized and quasi-randomized controlled trials.
Data collection and analysis
We independently identified eligible trials, assessed trial methodological quality and extracted data.
Two studies met the inclusion criteria. Method of generation of allocation sequence, concealment of allocation and blinding were unclear in both studies. A total of 134 children were allocated to three treatment groups comprising diazepam alone, phenobarbitone and chlorpromazine, or phenobarbitone and chlorpromazine and diazepam.
Meta-analysis of in-hospital deaths indicates that children treated with diazepam alone had a better chance of survival than those treated with combination of phenobarbitone and chlorpromazine (Relative Risk for death 0.36; 95% confidence interval 0.15 to 0.86; Risk Difference -0.22; 95% CI -0.38 to -0.06).
Giving diazepam alone, or supplementing conventional anticonvulsants (phenobarbitone and chlorpromazine) with diazepam, was reported in one study to be associated with a statistically significantly milder clinical course and shorter duration of hospitalization.
Although this review suggests that diazepam alone compared with combination of phenobarbitone and chlorpromazine may be more effective in treating tetanus, the small size, methodological limitations and lack of data on drug safety from available trials preclude definite conclusions to support change in current clinical practice. The application of this observation should be moderated by local needs and circumstances, pending the availability of better evidence. We recommend a reinforcement of preventive measures against tetanus infection and it is hoped that in the light of clear evidence about the preventive efficacy of tetanus toxoid immunization, concerted efforts should be made towards preventive interventions and ultimate eradication such that there will not be enough case materials for a trial. In the event of a need for a trial, a large prospective, multicenter, randomized controlled trial, which compares diazepam alone with combinations of other drugs (excluding diazepam) will be ideal.
Plain language summary
Diazepam for treating tetanus
Tetanus is a disease caused by bacteria (Clostridium tetani) found in soil and faeces. It can be immunised against but continues to kill children and adults. Newborn infants are the most vulnerable, particularly in Bangladesh, India, Indonesia, Nigeria and Pakistan, mainly because of unhygienic umbilical cord practices. Puncture wounds, burns, multiple ear piercing, tattooing and circumcision (male and female) can also cause tetanus infection. The symptoms include a sudden onset of muscle stiffness and spasms (involuntary contractions) in the neck, jaw and back, sufficient to cause rigid arching of the back. Glottal and laryngeal spasms may result in fluid being sucked into the breathing passages (aspiration) or inability to breathe (asphyxiation). These spasms progress over two weeks and recovery then takes some four weeks. Complications of the disease or its treatment include depressed breathing, extrapyramidal signs that mimic the tetanus spasms and rigidity, body (autonomic) dysfunction and pneumonia. Supportive nursing, nutritional support and physiotherapy are important. Mechanical ventilation is rarely available in resource poor countries to treat total paralysis. Drugs are needed to reducing the muscle spasms and rigidity, antibiotics to kill the bacteria and tetanus immunoglobulin to remove the toxins in the body. Diazepam has anticonvulsant, muscle relaxant, sedative and anxiety reducing effects. Diazepam treatment was associated with fewer deaths than was treatment with a combination of phenobarbitone and chlorpromazine. Combination treatments with diazepam did not give any further benefit (and may cause harm). The review authors searched the medical literature and identified two randomised controlled trials with a total of 134 hospitalized neonates and older children who had tetanus from Nigeria (19 neonates, seven children aged between one month and 10 years of age) and Indonesia (74 neonates, 34 children aged between three days and 12 years). All drugs were given orally as medications and feeds are usually given via nasogastric tube in the settings where the disease burden is high. Neither study provided information on the safety of the interventions or followed up survivors beyond discharge from hospital.
我們搜尋了Cochrane Neonatal Group trials register (June 2004), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to June 2004), EMBASE (1980 to June 2004), LILACS (2004), CINAHL (June 2004), Science Citation Index, African Index Medicus，會議摘要和文末的參考資料。我們使用私人通訊聯絡了在這個領域的研究者、專家和機構。
有兩個研究符合收納標準，但世代、隱匿性的分配和是否有單雙盲皆不清楚。總共有134個孩童分配到三個治療組，比較diazepam、phenobarbitone＋chlorpromazine和phenobarbitone＋chlorpromazine＋diazepam。用metaanalysis來比較住院的死亡率，結果顯示單獨使用diazepam比使用diazepam+phenobarbitone或diazepam+phenobarbitone+chlorpromazine有較好的生存機會。 死亡的RR:0.36，95%CI是0.15 – 0.86。RD:−0.22; 95%CI0.38 to −0.06)。有份報告指出單獨給予diazepam或搭配著傳統抗痙攣藥物(phenobarbitone and chlorpromazine)一起給予，有較輕微的臨床表現和較短的住院天術。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。