Dataset Information

A randomised controlled trial of two infusion rates to decrease reactions to antivenom.

ABSTRACT:

Background

Snake envenoming is a major clinical problem in Sri Lanka, with an estimated 40,000 bites annually. Antivenom is only available from India and there is a high rate of systemic hypersensitivity reactions. This study aimed to investigate whether the rate of infusion of antivenom reduced the frequency of severe systemic hypersensitivity reactions.

Methods and findings

This was a randomized comparison trial of two infusion rates of antivenom for treatment of non-pregnant adult patients (>14 y) with snake envenoming in Sri Lanka. Snake identification was by patient or hospital examination of dead snakes when available and confirmed by enzyme-immunoassay for Russell's viper envenoming. Patients were blindly allocated in a 11 randomisation schedule to receive antivenom either as a 20 minute infusion (rapid) or a two hour infusion (slow). The primary outcome was the proportion with severe systemic hypersensitivity reactions (grade 3 by Brown grading system) within 4 hours of commencement of antivenom. Secondary outcomes included the proportion with mild/moderate hypersensitivity reactions and repeat antivenom doses. Of 1004 patients with suspected snakebites, 247 patients received antivenom. 49 patients were excluded or not recruited leaving 104 patients allocated to the rapid antivenom infusion and 94 to the slow antivenom infusion. The median actual duration of antivenom infusion in the rapid group was 20 min (Interquartile range[IQR]:20-25 min) versus 120 min (IQR:75-120 min) in the slow group. There was no difference in severe systemic hypersensitivity reactions between those given rapid and slow infusions (32% vs. 35%; difference 3%; 95%CI:-10% to +17%;p = 0.65). The frequency of mild/moderate reactions was also similar. Similar numbers of patients in each arm received further doses of antivenom (30/104 vs. 23/94).

Conclusions

A slower infusion rate would not reduce the rate of severe systemic hypersensitivity reactions from current high rates. More effort should be put into developing better quality antivenoms.

Trial registration

www.slctr.lk SLCTR/2007/005.

SUBMITTER: Isbister GK

PROVIDER: S-EPMC3377702 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

A randomised controlled trial of two infusion rates to decrease reactions to antivenom.

Isbister Geoffrey K GK Shahmy Seyed S Mohamed Fahim F Abeysinghe Chandana C Karunathilake Harendra H Ariaratnam Ariaranee A

PloS one 20120618 6

<h4>Background</h4>Snake envenoming is a major clinical problem in Sri Lanka, with an estimated 40,000 bites annually. Antivenom is only available from India and there is a high rate of systemic hypersensitivity reactions. This study aimed to investigate whether the rate of infusion of antivenom reduced the frequency of severe systemic hypersensitivity reactions.<h4>Methods and findings</h4>This was a randomized comparison trial of two infusion rates of antivenom for treatment of non-pregnant ad ...[more]

PMID: 22719932

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Project description:BackgroundCurrently, there is inadequate evidence on which to base clinical management of neurotoxic snakebite envenoming, especially in the choice of initial antivenom dosage. This randomised controlled trial compared the effectiveness and safety of high versus low initial antivenom dosage in victims of neurotoxic envenoming.Methodology/ principal findingsThis was a balanced, randomised, double-blind trial that was conducted in three health care centers located in the Terai plains of Nepal. Participants received either low (two vials) or high (10 vials) initial dosage of Indian polyvalent antivenom. The primary composite outcome consisted of death, the need for assisted ventilation and worsening/recurrence of neurotoxicity. Hourly evaluations followed antivenom treatment. Between April 2011 and October 2012, 157 snakebite victims were enrolled, of which 154 were analysed (76 in the low and 78 in the high initial dose group). Sixty-seven (43·5%) participants met the primary outcome definition. The proportions were similar in the low (37 or 48.7%) vs. high (30 or 38.5%) initial dose group (difference = 10·2%, 95%CI [-6·7 to 27·1], p = 0·264). The mean number of vials used was similar between treatment groups. Overall, patients bitten by kraits did worse than those bitten by cobras. The occurrence of treatment-related adverse events did not differ among treatment groups. A total of 19 serious adverse events occurred, including seven attributed to antivenom.ConclusionsThis first robust trial investigating antivenom dosage for neurotoxic snakebite envenoming shows that the antivenom currently used in Nepal performs poorly. Although the high initial dose regimen is not more effective than the low initial dose, it offers the practical advantage of being a single dose, while not incurring higher consumption or enhanced risk of adverse reaction. The development of new and more effective antivenoms that better target the species responsible for bites in the region will help improve future patients' outcomes.Trial registrationThe study was registered on clinicaltrials.gov (NCT01284855) (GJ 5/1).

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Project description:Detection of asymptomatic adnexal tumours in postmenopausal women has increased due to wider use of diagnostic ultrasound and imaging quality improvements. Reliable methods to differentiate between benign and malignant tumours are required to avoid delays in treating ovarian cancer and to prevent unnecessary interventions for benign lesions. In the UK, the Royal College of Obstetricians and Gynaecologists has issued guidance for the management of adnexal cysts in postmenopausal women, which is considered standard in routine clinical practice. The protocol utilises the Risk of Malignancy Index to assess the risk of adnexal lesion being malignant. This protocol has a relatively high intervention rate in order to avoid a delay in a cancer diagnosis. The Simple Rules Protocol designed by International Ovarian Tumour Analysis Group reports a low false-positive rate in the diagnosis of ovarian cancer without a loss of sensitivity and therefore has the potential to reduce unnecessary interventions in asymptomatic postmenopausal women with benign cysts. 140 postmenopausal women aged 40-80, with incidentally detected adnexal tumours on ultrasound scan will be recruited to this study. They will be randomly allocated, to be assessed and managed according to either of the two protocols under investigation. In both arms of the study the tumours will be classified into three groups: high, intermediate or low risk of malignancy. Women with high risk of malignancy will be referred for management in a tertiary cancer centre, women with low-risk tumours will be managed expectantly, while those with intermediate risk findings have surgery in their local hospital units. Analysis will be on an intention-to-treat basis. Research ethical approval was granted by the North London Research Ethical Committee 2 (10/H0724/48). Trial results will be published according to the CONSORT statement. Registration at http://www.controlled-trials.com/ISRCTN89034131/. ISRCTN89034131.

Project description:BACKGROUND:Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades. METHODS:We conducted a 13-center, randomized, controlled trial that examined the effects of the rate of administration and the sodium chloride content of intravenous fluids on neurologic outcomes in children with diabetic ketoacidosis. Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design (0.9% or 0.45% sodium chloride content and rapid or slow rate of administration). The primary outcome was a decline in mental status (two consecutive Glasgow Coma Scale scores of <14, on a scale ranging from 3 to 15, with lower scores indicating worse mental status) during treatment for diabetic ketoacidosis. Secondary outcomes included clinically apparent brain injury during treatment for diabetic ketoacidosis, short-term memory during treatment for diabetic ketoacidosis, and memory and IQ 2 to 6 months after recovery from diabetic ketoacidosis. RESULTS:A total of 1389 episodes of diabetic ketoacidosis were reported in 1255 children. The Glasgow Coma Scale score declined to less than 14 in 48 episodes (3.5%), and clinically apparent brain injury occurred in 12 episodes (0.9%). No significant differences among the treatment groups were observed with respect to the percentage of episodes in which the Glasgow Coma Scale score declined to below 14, the magnitude of decline in the Glasgow Coma Scale score, or the duration of time in which the Glasgow Coma Scale score was less than 14; with respect to the results of the tests of short-term memory; or with respect to the incidence of clinically apparent brain injury during treatment for diabetic ketoacidosis. Memory and IQ scores obtained after the children's recovery from diabetic ketoacidosis also did not differ significantly among the groups. Serious adverse events other than altered mental status were rare and occurred with similar frequency in all treatment groups. CONCLUSIONS:Neither the rate of administration nor the sodium chloride content of intravenous fluids significantly influenced neurologic outcomes in children with diabetic ketoacidosis. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration; PECARN DKA FLUID ClinicalTrials.gov number, NCT00629707 .).

Dataset Information

A randomised controlled trial of two infusion rates to decrease reactions to antivenom.

Background

Methods and findings

Conclusions

Trial registration

Publications

A randomised controlled trial of two infusion rates to decrease reactions to antivenom.

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