Corticosteroids for treating dengue shock syndrome

  • Review
  • Intervention

Authors


Abstract

Background

Dengue shock syndrome is the most severe from of dengue haemorrhagic fever, one of the leading causes of death in children. Observational studies have suggested corticosteroids may benefit people with dengue shock syndrome.

Objectives

To compare corticosteroids with placebo or no corticosteroids for treating dengue shock syndrome.

Search methods

We searched the Cochrane Infectious Disease Group Specialized Register (August 2009), CENTRAL (The Cochrane Library 2009, Issue 2), MEDLINE (1966 to August 2009), EMBASE, (1974 to August 2009), LILACS (1982 to August 2009), and reference lists. We also contacted researchers.

Selection criteria

Randomized and quasi-randomized controlled trials comparing corticosteroids with no corticosteroids or placebo in people diagnosed with dengue shock syndrome.

Data collection and analysis

Two authors independently applied the inclusion criteria, extracted data, and assessed methodological quality. We calculated the risk ratio (RR) for dichotomous data and mean difference for continuous data, and presented them with 95% confidence intervals (CI).

Main results

Four trials involving 284 participants met the inclusion criteria. Corticosteroids were no more effective than placebo or no treatment for reducing the number of deaths (RR 0.68, 95% CI 0.42 to 1.11; 284 participants, 4 trials), the need for blood transfusion (RR 1.08, 0.52 to 2.24; 89 participants, 2 trials), or the number of serious complications (convulsions and pulmonary haemorrhage) as reported in one trial (63 participants).

Authors' conclusions

There is insufficient evidence to justify the use of corticosteroids in managing dengue shock syndrome. As corticosteroids can potentially do harm, clinicians should not use them unless they are participating in a randomized controlled trial comparing corticosteroids with placebo.

摘要

背景

皮質類固醇對於登革休克症候群的治療

登革休克症候群是最嚴重的登革出血熱,為一造成兒童死亡的原因。觀察性的研究發現皮質類固醇可能在治療登革休克症候群有一些助益。

目標

比較皮質類固醇與安慰劑或無皮質類固醇在治療登革休克症候群的表現。

搜尋策略

我們搜尋Cochrane Infectious Disease Group Specialized Register (2006年1月), CENTRAL(The Cochrane Library 2005年, Issue 4), MEDLINE (1966年 to2006年1月), EMBASE, (1974年 to 2006年1月), LILACS (1982年 to 2006年1月), 與參考文獻,我們也與研究者進行討論。

選擇標準

隨機和半隨機對照試驗比較:有皮質類固醇與沒有皮質類固醇或安慰劑在診斷為登革休克症候群病人的治療。

資料收集與分析

兩位作者獨立地提出納入標準、摘錄數據,並評估試驗的品質。我們從數據中計算出RR和加權平均差異評估連續性數據,並表現出其95%信賴區間。

主要結論

4個臨床試驗包括284名受試者符合納入標準,皮質類固醇相對於安慰劑或不治療的病人在減少死亡人數方面,沒有比較有效(4個臨床試驗,RR 0.68 , 95 %CI:0.42 – 1.11 ; 284名受試者);在需要輸血方面,沒有比較有效(2個臨床試驗,89名受試者,RR 1.08,95 % CI:0.52 – 2.24);或一些嚴重的併發症(抽搐和肺出血)方面,沒有比較有效(1個臨床試驗,63名受試者)。

作者結論

沒有足夠的證據證明使用皮質類固醇可以治療登革休克症候群;皮質類固醇有潛在的危害,臨床醫生不應該使用它們,由於皮質類固醇的使用有潛在危險,因此除非醫師正在參與比較皮質類固醇與安慰劑療效的隨機臨床試驗,不然就不應該使用該藥物。

翻譯人

本摘要由三軍總醫院楊登和翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

沒有很好的證據可以顯示皮質類固醇有利於在登革休克症候群的治療;登革熱病毒是由蚊蟲傳播,並可能導致輕微發燒或包括發燒與出血在內更嚴重的疾病(登革出血熱)。出血的症狀一般是在皮膚可看見微小紅斑,但偶爾會更嚴重的情形會影響到鼻子、牙齦和腸道。最嚴重情況能夠引起休克、虛脫,甚至死亡(登革休克症候群),目前的治療登革休克症候群,是直接給予足夠輸液治療,但皮質類固醇已被建議作為藥物使用,因其抗發炎反應有幫助。這個臨床試驗的綜論只有包括4個品質不佳的小試驗(284名受試者),並且顯示沒有任何助益。應該在些藥物使用前,需要更進一步的臨床試驗;由於此類藥物有抑制免疫系統的情形,有可能會有一些副作用,可能因為免疫抑制的緣故而讓病人遭受其他的感染。

Résumé

Corticostéroïdes pour le traitement de la dengue à syndrome de choc

Contexte

La dengue à syndrome de choc est la forme la plus sévère de dengue hémorragique, l'une des premières causes de décès chez l'enfant. Des études observationnelles ont suggéré que les corticostéroïdes pourraient être bénéfiques chez les patients atteints de dengue à syndrome de choc.

Objectifs

Comparer des corticostéroïdes à un placebo ou à une absence de corticostéroïdes dans le traitement de la dengue à syndrome de choc.

Stratégie de recherche documentaire

Nous avons consulté le registre spécialisé du groupe Cochrane sur les maladies infectieuses (août 2009), CENTRAL (Bibliothèque Cochrane 2009, numéro 2), MEDLINE (1966 à août 2009), EMBASE (1974 à août 2009), LILACS (1982 à août 2009) ainsi que les références bibliographiques. Nous avons également contacté des chercheurs.

Critères de sélection

Les essais contrôlés randomisés et quasi-randomisés comparant des corticostéroïdes à une absence de corticostéroïdes ou à un placebo chez des patients présentant un diagnostic de dengue à syndrome de choc.

Recueil et analyse des données

Deux auteurs ont appliqué les critères d'inclusion, extrait les données et évalué la qualité méthodologique des essais de manière indépendante. Nous avons calculé le risque relatif (RR) pour les données dichotomiques, et la différence moyenne (DM) pour les données continues, avec des intervalles de confiance (IC) à 95 % dans les deux cas.

Résultats Principaux

Quatre essais portant sur 284 participants remplissaient les critères d'inclusion. Les corticostéroïdes n'étaient pas plus efficaces que le placebo ou l'absence de traitement pour réduire le nombre de décès (RR de 0,68, IC à 95 %, entre 0,42 et 1,11 ; 284 participants, 4 essais), le recours à une transfusion sanguine (RR de 1,08, entre 0,52 et 2,24 ; 89 participants, 2 essais), ou le nombre de complications graves (convulsions et hémorragie pulmonaire) dans un essai (63 participants).

Conclusions des auteurs

Les preuves sont insuffisantes pour justifier l'utilisation de corticostéroïdes dans la prise en charge de la dengue à syndrome de choc. Les corticostéroïdes étant associés à des effets délétères potentiels, les cliniciens devraient limiter leur utilisation au contexte d'un essai contrôlé randomisé comparant des corticostéroïdes à un placebo.

Plain language summary

No good evidence that corticosteroids are helpful in dengue shock syndrome

The dengue virus is transmitted by mosquitoes and can cause either a mild illness with fever or a more severe illness with fever and bleeding (dengue haemorrhagic fever). The bleeding is generally seen as tiny red spots on the skin but can occasionally be more severe affecting the nose, gums, and gut. In its most severe form it can cause shock, collapse, and sometimes death (dengue shock syndrome). The current treatment for dengue shock syndrome is to give fluids directly into the bloodstream, but corticosteroids have been suggested as drugs that may help due to their anti-inflammatory properties. This review of trials found only four small trials (with 284 participants) that were not of good quality and which showed no benefit overall. Further trials would be needed before this drug were used in these patients, as there is the potential for adverse effects due to the drugs' properties of suppressing the immune system and potentially leaving people open to other infections.

Résumé simplifié

Corticostéroïdes pour le traitement de la dengue à syndrome de choc

Aucune preuve de bonne qualité n'indique que les corticostéroïdes sont utiles dans la dengue à syndrome de choc.

Le virus de la dengue est transmis par les moustiques, et peut entraîner une maladie légère accompagnée de fièvre ou une maladie plus sévère accompagnée de fièvre et de saignements (dengue hémorragique). Les saignements se présentent généralement sous forme de minuscules points rouges sur la peau, mais peuvent parfois être plus sévères et affecter le nez, les gencives et l'intestin. Dans sa forme la plus grave, la maladie peut entraîner un choc et un malaise, et peut parfois entraîner le décès du patient (dengue à syndrome de choc). À l'heure actuelle, la dengue à syndrome de choc est traitée en administrant des fluides directement dans le courant sanguin, mais il a été suggéré que les corticostéroïdes pourraient être utiles en raison de leurs propriétés anti-inflammatoires. Cette revue des essais n'a identifié que quatre petits essais (portant sur 284 participants), qui n'étaient pas de bonne qualité et ne rapportaient aucun bénéfice global. D'autres essais sont nécessaires avant que ces médicaments ne puissent être utilisés chez ces patients, car leurs propriétés immunosuppressives peuvent entraîner des effets indésirables potentiels et exposer les patients à d'autres infections.

Notes de traduction

Traduit par: French Cochrane Centre 1st April, 2013
Traduction financée par: Pour la France : Minist�re de la Sant�. Pour le Canada : Instituts de recherche en sant� du Canada, minist�re de la Sant� du Qu�bec, Fonds de recherche de Qu�bec-Sant� et Institut national d'excellence en sant� et en services sociaux.

Background

Definition

Dengue virus is an arbovirus transmitted to humans by two species of mosquito, Aedes aegypti and A. albopictus. The four serotypes of dengue virus can cause a wide range of symptoms from mild febrile illness to severe haemorrhagic fever, which leads to dengue shock syndrome. Dengue haemorrhagic fever is said to be present when patients have high fever for two to seven days, bleeding, enlargement of the liver, and insufficient circulation (Nimmanitya 1993). Bleeding usually occurs and frequently presents as tiny, scattered, red spots in the skin (petechiae). Bleeding from the nose, gums, and gastrointestinal tract is less common but may be severe. There are four grades dengue haemorrhagic fever according to the level of shock or bleeding: grades I and II are non-shock dengue haemorrhagic fever, and grades III and IV are cases with shock (dengue shock syndrome) (WHO 1997).

Epidemiology

Dengue haemorrhagic fever was first recognized in South-East Asia in the 1950s when outbreaks occurred in Philippines, Thailand, and Vietnam. The incidence of dengue haemorrhagic fever has increased in several countries in Asia and is one of the leading causes of death in children (Thongcharoen 1993). It is currently estimated that the majority of the 100 million cases of dengue infection that occur annually are in South-East Asia (Kautner 1997). Dengue haemorrhagic fever is also endemic in some parts of the Americas. Twenty-five countries in the Americas reported 42,246 cases of dengue haemorrhagic fever and 582 deaths between 1981 and 1996 (Pinheiro 1997), and an epidemic occurred in Cuba in 1981. There are increasing numbers of imported cases of dengue infection among travellers returning from these endemic areas (Kautner 1997).

Pathogenesis

It is unclear how dengue infection causes bleeding and shock. Immune responses seem to play an important role in causing illness. Infection with one of the four serotypes of dengue virus provides lifelong immunity to that serotype. Secondary infection with another serotype of dengue virus can form a 'virus-antibody complex' by combining with existing antibody from previous dengue infection. The virus-antibody complex promotes the growth of the virus in mononuclear cells and activates the complement system (Halstead 1993). In another hypothesis, genetic changes in the virus genome increase viral replication, virulence, and epidemic potential of the dengue virus (Gubler 1998). Capillary damage and increased permeability of vessel walls cause plasma to flow into extravascular spaces and increase the blood concentration. A depletion of plasma volume can cause low blood pressure and lead to shock in severe cases. Bleeding in dengue haemorrhagic fever is related to platelet depletion (thrombocytopenia, ≤ 100,000 platelets/mm3), which results from the depression of megakaryocyte function and increased destruction of mature platelets. It may also be involved with microvascular injury, platelet dysfunction, and clotting defect in blood vessels (disseminated intravascular coagulation) (Nelson 1964; Mitrakul 1979). Complications such as encephalopathy, hepatic failure, and renal failure can occur but are unusual.

Management

The standard treatment of dengue shock syndrome is to immediately administer intravenous fluids to expand plasma volume. People are at particular risk of circulatory problems when their fever resolves. Plasma leakage is thought to be self limiting and rarely lasts longer than 48 hours, so clinicians prevent shock by replacing the plasma volume as soon as the haematocrit concentration starts to rise (Nimmanitya 1993). Clinicians give blood if patients are bleeding. There are no drugs available specifically for the treatment of dengue haemorrhagic fever. Although carbazochrome sodium sulfonate (AC-17) was tested in clinical trials because it is thought to be protective against vascular damage and decrease the severity of plasma leakage, the authors of one study concluded no benefit was shown (Tassniyom 1997).

Corticosteroids are potent anti-inflammatory agents that have a wide range of effects on immunological processes and have found use in a broad spectrum of diseases (Kehrl 1983). The use of corticosteroids in the management of dengue haemorrhagic fever and dengue shock syndrome is under debate. The World Health Organization does not mention corticosteroids in the treatment guidelines for dengue shock syndrome (WHO 1997). Observational studies in Thailand have shown a marked decline in case-mortality rate without any use of corticosteroids; this was attributed to both close observation of the patients for signs of shock during the critical period and early replacement of plasma loss (Cohen 1964; Nimmanitya 1978). Corticosteroids are used in some countries, particularly those in South-East Asia for managing dengue shock syndrome. They are thought to be effective for stabilizing capillary permeability and have been used in addition to fluid replacement (Sumarmo 1987). This systematic review examines the best available evidence on the effects of corticosteroids on death in dengue shock syndrome.

Objectives

To compare corticosteroids with placebo or no corticosteroids for treating dengue shock syndrome.

Methods

Criteria for considering studies for this review

Types of studies

Randomized and quasi-randomized controlled trials.

Types of participants

People diagnosed with dengue shock syndrome, as defined by the trial authors.

Types of interventions

Intervention

Corticosteroids (methylprednisolone, hydrocortisone, dexamethasone).

Control

Placebo or no corticosteroids.

Types of outcome measures

Primary

Death.

Secondary
  • Time to regain normal blood pressure.

  • Intravenous fluid requirement during the period of shock.

  • Blood transfusion.

  • Severe complications, including pulmonary oedema, renal failure, hepatic failure, pulmonary haemorrhage and convulsion.

  • Days in hospital.

  • Adverse events.

Search methods for identification of studies

We attempted to identify all relevant trials regardless of language or publication status (published, unpublished, in press, and in progress).

Databases

We searched the following databases using the search terms and strategy described in Appendix 1: Cochrane Infectious Diseases Group Specialized Register (August 2009); Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library (2009, Issue 2); MEDLINE (1966 to August 2009); EMBASE (1974 to August 2009); and LILACS (1982 to August 2009).

Researchers

We contacted individual researchers working in the field for unpublished trials.

Reference lists

We also checked the reference lists of all studies identified by the above methods.

Data collection and analysis

Selection of studies

Two authors independently screened the results of the literature search for potentially relevant trials. We used an eligibility form to assess these trials for inclusion in the review; the reasons for excluding studies are in the 'Characteristics of excluded studies'.

Data extraction and management

We used data extraction forms to collect information on the participants, methods, interventions, and outcomes. The first two authors independently extracted data. Where there were differences, we referred to the original papers. We checked the data sources to avoid extracting data from multiple publications based on the same data set.

Assessment of risk of bias in included studies

Two authors independently assessed generation of allocation sequence and allocation concealment as adequate, inadequate, or unclear (Jüni 2001). We also described who was blinded, and assessed the inclusion of all randomized participants in the final analysis to be adequate if 90% or more.

Data synthesis

We used Review Manager 5 for data analysis. We combined dichotomous data using risk ratio (RR) and combined continuous data using mean difference (MD), both with 95% confidence intervals (CI).

We assessed heterogeneity by visually examining the forest plots and by using the chi-squared test for heterogeneity with a 10% level of statistical significance. The I2 statistic was also used to measure inconsistency results among trials (Higgins 2003). We intended to explore disease severity and corticosteroid dose and type as potential sources of heterogeneity, but there were too few trials.

Results

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

Four randomized controlled trials involving 284 participants met the inclusion criteria (see 'Characteristics of included studies') and four were excluded (see 'Characteristics of excluded studies').

Trial location and participants

Two trials were conducted in Thailand (Pongpanich 1973; Tassniyom 1993), one in Burma (now known as Myanmar) (Min 1975), and one in Indonesia (Sumarmo 1982). Participants were children aged less than 15 years with serologically confirmed dengue and shock.

Interventions

Three trials compared intravenous hydrocortisone hemisuccinate with no corticosteroids or placebo (Pongpanich 1973; Min 1975; Sumarmo 1982), and one compared methyl prednisolone with placebo (Tassniyom 1993).

Outcomes

All four trials reported on death (Pongpanich 1973; Min 1975; Sumarmo 1982; Tassniyom 1993), two reported the number needing a blood transfusion (Pongpanich 1973; Tassniyom 1993), and one reported the duration of hospitalization (Tassniyom 1993).

Risk of bias in included studies

Also see Table 1 and the ' Characteristics of included studies '.

Generation of allocation sequence was adequate in one trial. No trials described allocation concealment, three trials used double blinding, and the same three trials were adequate for the number of randomized participants included in the analysis.

Table 1. Risk of bias assessment
  1. aInclusion of all randomized participants in the final analysis.

TrialAllocation sequence generationAllocation concealmentBlindingInclusiona
Min 1975UnclearUnclear"double blind"Adequate
Pongpanich 1973UnclearInadequateNoneInadequate
Sumarmo 1982UnclearUnclear"double blind"Adequate
Tassniyom 1993AdequateUnclear"double blind"Adequate

Effects of interventions

Death

Death was an outcome in all four trials, but only three reported deaths (Min 1975; Sumarmo 1982; Tassniyom 1993). Overall no benefit of corticosteroids was demonstrated, but the number of participants in the analysis was small (284 participants, Analysis 1.1).

Blood transfusion

There was no statistically significant difference in the number of participants needing blood transfusion (89 participants, 2 trials,Analysis 1.2) (Pongpanich 1973; Tassniyom 1993).

Complications

Tassniyom 1993 reported no statistically significant difference between the corticosteroids and placebo for convulsions and pulmonary haemorrhage (63 participants, Analysis 1.3).

Days in hospital

Tassniyom 1993 reported an average stay of 6.2 days in the placebo group and 7.3 days in the corticosteroid group (63 participants, Analysis 1.4).

Discussion

Trials in people with a life-threatening illness are not easy to conduct, and the authors of these trials did their best to ensure an unbiased comparison. However, the trials were conducted some time ago and methods have become more advanced and more stringent. In the context of current standards, these trials have potential for bias, as allocation was not clearly concealed in any of them. Four trials were included in the review and the results showed no benefits of corticosteroids in reducing death in dengue shock syndrome.

Authors' conclusions

Implications for practice

There is insufficient evidence to justify the use of corticosteroids in managing dengue shock syndrome. They should not be used in dengue shock syndrome outside the context of carefully conducted randomized controlled trials.

Implications for research

Large, randomized controlled trials that carefully conceal allocation and measure death as an outcome are required. Types, dose, and duration of corticosteroids should also be studied.

Acknowledgements

Ratana Panpanich developed the protocol for this review during the Fellowship Programme organized in May and June 2001 by the Cochrane Infectious Diseases Group. The UK Department for International Development (DFID) supported this Fellowship through the Effective Health Care Alliance Programme at the Liverpool School of Tropical Medicine.

This document is an output from a project funded by the DFID for the benefit of developing countries. The views expressed are not necessarily those of DFID.

Data and analyses

Download statistical data

Comparison 1. Corticosteroids versus no corticosteroids or placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Death4284Risk Ratio (M-H, Fixed, 95% CI)0.68 [0.42, 1.11]
2 Blood transfusion289Risk Ratio (M-H, Fixed, 95% CI)1.08 [0.52, 2.24]
3 Complications1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
3.1 Pulmonary haemorrhage1 Risk Ratio (M-H, Fixed, 95% CI)Not estimable
3.2 Convulsions1 Risk Ratio (M-H, Fixed, 95% CI)Not estimable
4 Days in hospital1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
Analysis 1.1.

Comparison 1 Corticosteroids versus no corticosteroids or placebo, Outcome 1 Death.

Analysis 1.2.

Comparison 1 Corticosteroids versus no corticosteroids or placebo, Outcome 2 Blood transfusion.

Analysis 1.3.

Comparison 1 Corticosteroids versus no corticosteroids or placebo, Outcome 3 Complications.

Analysis 1.4.

Comparison 1 Corticosteroids versus no corticosteroids or placebo, Outcome 4 Days in hospital.

Appendices

Appendix 1. Search methods: detailed search strategies

Search setCIDG SRaCENTRALMEDLINEbEMBASEbLILACSb
1adrenal cortex hormoneadrenal cortex hormoneexp DENGUEexp DENGUEdengue
2corticosteroidscorticosteroidsdenguedenguecorticosteroids
3hydrocortisonehydrocortisoneHEMORRAGIC FEVERHEMORRAGIC FEVERdexamethasone
4dexamethasonedexamethasonehemorrhagic feverhemorrhagic feverprednisolone
5methylprednisolonemethylprednisolone('break-bone fever').ti,ab('break-bone fever').ti,ab2 or 3 or 4
6prednisoloneprednisolone1 or 2 or 3 or 4 or 51 or 2 or 3 or 4 or 51 and 5
7hemorrhagic feverhemorrhagic feverADRENAL CORTEX HORMONESadrenal cortex hormones
8dengue feverdengue fevercorticosteroidscorticosteroids
9steroid*steroid$
10cortisol*cortisol$
11HYDROCORTISONEHYDROCORTISONE
12hydrocortisonehydrocortisone
13DEXAMETHASONEDEXAMETHASONE
14dexamethasonedexamethasone
15METHYLPREDNISOLONEMETHYLPREDNISOLONE
16methylprednisolonemethylprednisolone
17PREDNISOLONEPREDNISOLONE
18prednisoloneprednisolone
197 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 187 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18
206 and 196 and 19
21Limit 20 to humanLimit 20 to human

aCochrane Infectious Diseases Group Specialized Register.
bSearch terms used in combination with the search strategy for retrieving trials developed by The Cochrane Collaboration (Higgins 2005; upper case: MeSH or EMTREE heading; lower case: free text term.

What's new

DateEventDescription
12 August 2009New search has been performedNew search conducted; no new trials for inclusion

History

Protocol first published: Issue 1, 2002
Review first published: Issue 3, 2006

DateEventDescription
19 September 2008AmendedConverted to new review format with minor editing.

Contributions of authors

All authors contributed to the development of the review, extraction of the data, analysis, and interpretation of the results.

Declarations of interest

None known.

Sources of support

Internal sources

  • Faculty of Medicine, Chiang Mai University, Thailand.

External sources

  • Department for International Development, UK.

Differences between protocol and review

The intravenous fluid requirement during the period of shock and blood transfusion were added as secondary outcomes measures as they are important supportive treatments in both groups. The amounts of fluids and blood requirements should be compared if they reported.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Min 1975

Methods

Generation of allocation sequence: participants were randomly selected after matching for age and sex

Allocation concealment: unclear

Blinding: "double blind"

Inclusion of randomized participants in analysis: "complete follow up"

Participants98 children diagnosed with dengue shock syndrome using serological confirmation
Interventions

1. Hydrocortisone hemisuccinate (Solucortef): intravenous in a single dose of 25 mg/kg on day 1, 15 mg/kg on day 2, and 10 mg/kg on day 3 in addition to fluid replacement; 48 participants
2. Fluid replacement only: 50 participants

Fluid replacement included normal saline, Ringer lactate solution, plasma, and blood products

Outcomes1. Death
2. Duration of shock
Notes

Location: children's hospital in Rangoon, Burma (now known as Myanmar)

Date: 1973-4

Haemagglutination inhibition test and complement fixation test performed on paired sera; positive result was a 4-fold rise in titre or a fixed level at 1:640 or more

Pongpanich 1973

Methods

Generation of allocation sequence: "a card was drawn" to decide which treatment programme participants entered; numbers recruited were unbalanced

Allocation concealment: inadequate

Blinding: none

Inclusion of randomized participants in analysis: "complete follow up"

Participants26 children diagnosed with dengue shock syndrome using serological confirmation
Interventions

1. Hydrocortisone hemisuccinate: intravenous 25 mg/kg/day; 5 mg/kg at start, rest given in divided doses every 4 to 6 h in addition to fluid replacement; 7 participants
2. Fluid replacement only: 19 participants

Fluid replacement included normal saline, albumin, dextrans, plasma, and blood products

Outcomes1. Death
2. Duration of shock
3. Requirement of fluid replacement
Notes

Location: Ramathibodi Hospital, Thailand

Date: 1969-71

Haemagglutination inhibition test and complement fixation test performed on paired sera; positive result was a 4-fold rise in titre or a fixed level at 1:640 or more

Sumarmo 1982

Methods

Generation of allocation sequence: a "simple random assignment"

Allocation concealment: unclear

Blinding: "double blind"

Inclusion of randomized participants in analysis: "complete follow up"

Participants97 children diagnosed with dengue shock syndrome using serological confirmation
Interventions1. Hydrocortisone hemisuccinate: 50 mg/kg, single intravenous dose in addition to fluid replacement; 47 participants
2. Fluid replacement with a placebo: sodium chloride 0.9% with same colour and turbidity; 50 participants
Outcomes1. Death
2. Duration of shock
Notes

Location: Indonesia

Date: 1978-9

Tassniyom 1993

Methods

Block randomization Generation of allocation sequence: generated by statistician and running number put on drug package

Allocation concealment: unclear

Blinding: "double blind"

Inclusion of randomized participants in analysis: "complete follow up"

Participants63 children diagnosed with dengue shock syndrome using World Health Organization clinical criteria and serological confirmation
Interventions1. Methyl-prednisolone sodium succinate (Solu-medrol, Upjohn): single dose of 30 mg/kg in addition to fluid replacement; 32 participants
2. Fluid replacement with a placebo: 5% dextrose in normal saline solution; 31 participants
Outcomes1. Death
2. Number of needing transfusion
3. Number of complication
4. Duration of hospitalization
Notes

Location: Khon Kaen, Thailand

Date: 1987-8

Haemagglutination inhibition test and enzyme-linked immunosorbent assay

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Futrakul 1981Not a randomized controlled trial
Futrakul 1987Not a randomized controlled trial
Sumarmo 1975Not a randomized controlled trial
Sumarmo 1987Review of studies on the role of steroids on dengue shock syndrome

Ancillary