Propofol versus thiopental sodium for the treatment of refractory status epilepticus (Review)

Authors


Abstract

Background

Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome.

Objectives

To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol.

Search methods

We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals).

Selection criteria

All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol.

Data collection and analysis

Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications.

Main results

One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months.

Authors' conclusions

There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. There is a need for large, randomised controlled trials for this serious condition.

Plain Language Summary

Propofol versus thiopental sodium for the treatment of refractory status epilepticus

Persistent convulsions are a major medical emergency associated with significant morbidity and mortality. At times, these convulsions fail to respond to first- and second-line drug therapy and may be observed in up to 31% of patients suffering from persistent seizure or convulsive activities. Persistent seizure activity may become refractory to antiepileptic drugs. Anaesthetics such as thiopental sodium and propofol are frequently given for control of seizures in such situations. Both agents have inherent side effects and complications. This review appraises the evidence for the these anaesthetic drugs in controlling seizure activity in patients with RSE.

There is a lack of good-quality evidence to support the choice of anaesthetic drug for the treatment of patients with RSE. Only one trial could be identified, which was terminated early due to recruitment problems. The two drugs did not show any difference among each other. The only difference noted was the requirement of prolonged mechanical ventilation for patients in the thiopental group. This could be due to the long half-life of the drug. There is a clear need for a large randomised controlled trial to study the efficacy of anaesthetic agents in the treatment of RSE.

Background

Status epilepticus (SE) is defined as a condition in which there is either continuous seizure activity for more than 30 minutes, or two or more seizure activities in a sequence without return of full consciousness between the episodes (Prasad 2005; Working Group 1993). There is no universally accepted definition of SE. There is no consensus on the duration of seizure activity that may be required to define SE. SE may be broadly classified in two types, convulsive and non-convulsive. The common aetiologies for SE are stroke, traumatic brain injury, brain tumours, central nervous system infection, metabolic or toxic encephalopathies and electrolyte disorders. SE is a major medical emergency associated with significant morbidity and mortality (16% to 23%). Refractory status epilepticus (RSE) is defined as SE that fails to respond to first- and second-line therapy and it is observed in 9% to 31% of patients with SE (Mayer 2002; Treiman 1998). To be categorised as RSE, some authors have suggested a time frame (Mayer 2002), whereas others have not (Holtkamp 2007; Rossetti 2005). The first line of treatment for SE includes benzodiazepines; the second line includes antiepileptic drugs such as phenytoin, phenobarbital or valproic acid. Assistance of an anaesthetist is required for managing RSE, where coma may be induced with anaesthetic agents in order to achieve complete control of seizures. The use of anaesthetic agents such as thiopental sodium and propofol for managing RSE is common in many centres (Parviainen 2002; Van Gestel 2005). Thiopental sodium belongs to barbiturates group of drugs unrelated to propofol, which is a phenolic compound. Both agents have been found to be effective in controlling seizures in RSE (Parviainen 2002; Van Gestel 2005). There is substantial lack of evidence as to which of the two drugs, thiopental sodium and propofol, is better in terms of clinical outcome of patients with RSE. In a systematic review published in 2002 by Claassen 2002, the authors compared the efficacy of midazolam, propofol and pentobarbital for terminating seizures in RSE patients. Considering all possible limitations, the authors concluded that pentobarbital was more effective than any other strategy suggested for treatment of RSE.

Description of the condition

RSE develops when patients become resistant to antiepileptic drugs with passage of time. In hospital-based series, it develops in 31% to 44% of patients with SE (Mayer 2002). Significant morbidity and mortality are associated with RSE. Failure to respond to antiepileptic drugs has led to the use of anaesthetic agents in controlling seizures. The popular anaesthetic agents are the barbiturates, propofol and isoflurane.

Description of the intervention

Anaesthetic agents have been used for the treatment of RSE. Barbiturates and propofol have been commonly used in this regard. However, most of the published literature is anecdotal. There is no consensus as to which of the two agents is better in terms of clinical outcome.

How the intervention might work

Thiopental sodium, a barbiturate, is a γ-aminobutyric acid-A (GABAA) agonist with possible actions on calcium channels (Rogowski 2004). Barbiturates have a prolonged duration of action, mainly due to their accumulation in the body. They are also known to produce hypotension during use. In contrast, propofol is gaining popularity because of its shorter duration of action and little tendency to accumulate in the body. Similar to barbiturates, propofol also produces hypotension, and reduces intracranial pressure and brain metabolic requirements (Marik 2004). Prolonged use of propofol as an infusion has been shown to result in potentially fatal cardiovascular collapse associated with lactic acidosis, hypertriglyceridaemia and rhabdomyolysis, the so-called "propofol infusion syndrome" (Zarovnaya 2007). Both agents are also N-methyl-D-aspartate (NMDA) antagonists in vitro (Zhan 2001).

Why it is important to do this review

The current literature provides enough evidence to suggest that both thiopental and propofol are effective in the treatment of RSE (Parviainen 2002; Van Gestel 2005). As both agents are associated with inherent side effects and complications, the choice of the agent is usually left at the discretion of the attending anaesthetist. There is a lack of evidence to suggest the superiority of one drug over the other. A systematic review of published literature would help us reach to some conclusion. To date, no Cochrane systematic review comparing thiopental and propofol for treatment of RSE has been published. The aim of this review is to establish which of the two commonly used anaesthetic agents, thiopental or propofol, is better suited for the treatment of RSE.

Objectives

To compare the efficacy, adverse effects, and short- and long-term outcomes of SE treated with one of the two anaesthetic agents, thiopental sodium or propofol.

Methods

Criteria for considering studies for this review

Types of studies

We included all relevant randomised or quasi-randomised controlled studies, regardless of blinding. Diagnosis of RSE was based on any given standard definition specified in the articles and treatment consisting either of propofol or thiopental sodium. We excluded studies that did not define RSE, prior treatment with any other intravenous anaesthetic before treatment with thiopental sodium or propofol and use of intermittent boluses of thiopental sodium or propofol for treating RSE.

Types of participants

We included individuals of any age group and gender diagnosed with RSE of any aetiology.

Types of interventions

Patients receiving either thiopental sodium or propofol for the treatment of RSE, in addition to standard antiepileptic drugs used in SE.

Types of outcome measures

Primary outcomes
  • 1.Total control of seizures.
  • 2.Mortality.
  • 3.Length of ICU stay.
Secondary outcomes
  • 1.Adverse events, such as infection, hypotension and propofol infusion syndrome.
  • 2.Duration of mechanical ventilatory support.
  • 3.Duration of hospital stay.
  • 4.Cognitive deficits.
  • 5.Long-term outcomes, such as dependence for daily activities (walking, eating, bathing, dressing and toileting).

Search methods for identification of studies

We searched the following databases:

  • 1.Cochrane Epilepsy Group Specialized Register (10 May 2012);
  • 2.The Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012) using the search strategy outlined in Appendix 1;
  • 3.MEDLINE (Ovid, 1946 to May week 1, 2012) using the search strategy outlined in Appendix 2.

We did not apply any language restrictions.

Searching other resources

We searched the following web sites for information about relevant ongoing trials:

  • 1.IndMED (www.indmed.nic.in) (10 May 2012) using the search terms: 'Propofol AND (thiopental OR thiopentone) AND (epilepsy OR epileptic)';
  • 2.South Asian Database of Controlled Clinical Trials (www.cochrane-sadcct.org, accessed 10 May 2012) using the search term 'propofol';
  • 3.www.Clinicaltrials.gov (10 May 2012), using the search term 'propofol' for condition 'epilepsy'.

Data collection and analysis

Selection of studies

Using the results of the above searches, we screened all titles and abstracts for eligibility. Two review authors (AB and GPS) independently performed this screening. We obtained and assessed the full articles of all eligible RCTs for relevance based on the pre-planned check-list. Each author documented the reason for each trial that was excluded. We resolved any disagreement between the two review authors by discussion with a third review author (HP), who decided on the inclusion or exclusion of the study. We compiled a list of all eligible trials.

Data extraction and management

Two review authors (AB and GPS) planned to independently extract the data and assess the trial quality. We resolved any disagreement through consultation with the third review author (HP). In case of additional information being required, AB was chosen to contact the first author of the relevant trial.

Assessment of risk of bias in included studies

Two review authors assessed the methodological quality of the eligible trials independently (AB and GPS). We resolved any disagreement by discussion with the third review author (HP). We performed the assessment as suggested in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008). We judged the quality of the study on the basis of the following:

  • 1.method of randomisation,
  • 2.concealment of allocation,
  • 3.blinding and outcome,
  • 4.incomplete outcome data,
  • 5.selective reporting,
  • 6.any other bias.

We included a 'Risk of bias' table as part of the 'Characteristics of included studies' and a 'Risk of bias summary' figure (Figure 1), which details all of the judgements made for all included studies in the review.

Figure 1.

Risk of bias graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies.

Measures of treatment effect

We planned to record the number (percentage) of participants experiencing each categorical outcome and mean (standard deviation (SD))/median (range) for continuous outcome per randomised group. All primary analyses were dealt by 'intention to treat'.

Unit of analysis issues

We planned to include only RCTs in our review with parallel design. The nature of the intervention here suggested that unit of analysis issues, such as those associated with cluster randomisation, were unlikely to arise. If we included any cluster randomised studies we planned to assess the risk of bias following the suggestions in Section 16.3.2 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008), and the approach to analysis suggested in the subsequent sections. We would have taken a similar approach to any cross-over trials included.

Dealing with missing data

We contacted the first author of the relevant trial and collect the required information.

Assessment of heterogeneity

We planned to assess the clinical heterogeneity of included studies as assessed as methodological diversity, such as distribution of patient characteristics (age, seizure type and number of drugs taken at the time of randomisation) and trial factors (randomisation concealment, blinding and loss to follow-up). We planned to use the Q statistics to test the statistical heterogeneity between trials and the I2 statistic to assess the magnitude of heterogeneity (Higgins 2002).

Assessment of reporting biases

We planned to assess publication bias/small-study effect in a qualitative manner, using a funnel plot. Due to limited data, we did not assess this bias.

Data synthesis

We quantitatively reviewed the included data and combined it by intervention, outcome and population using the Cochrane Collaboration's statistical software, Review Manager (RevMan 2011). We planned to assess statistical heterogeneity using the Chi2 statistic and consider P values of 0.05 or less as statistically significant. We planned to assess the level of inconsistency across the studies using the I2 statistic where I2 greater than 50% indicates substantial heterogeneity. Had we found statistically significant heterogeneity that we could not readily explain, we would have assessed it using a random-effects model.

Due to only one study meeting our inclusion criteria, we did not perform a meta-analysis.

Subgroup analysis and investigation of heterogeneity

We planned to perform subgroup analyses for the following: age groups (children (< 14 years of age) and adults), gender, aetiology and type of seizure (convulsive or non-convulsive).

Due to limited data, we did not perform a subgroup analysis.

Sensitivity analysis

We planned to perform a sensitivity analysis to assess the influence of including studies judged low in methodological quality and characteristic of intervention; that is, the doses of propofol and thiopental used.

Due to limited data, we did not perform a sensitivity analysis.

Results

Description of studies

See: Characteristics of included studies.

See: Characteristics of included studies

The study conducted by Rossetti et al (Rossetti 2011) was a randomised, single-blind, multicentre trial studying adults with RSE. Patients received either propofol or barbiturates for control of seizures. There primary end point was the proportion of patients with RSE controlled after first course of study drug and secondary end point included drug tolerability. The trial was terminated after three years with only 24 patients recruited of the 150 required. The trial was under-sampled and found prolonged mechanical ventilation requirement in the barbiturate arm. The treatment-related complications were comparable for both propofol and barbiturates.

Results of the search

Our searches yielded 34 references (eight from MEDLINE, three from CENTRAL, two from the Cochrane Epilepsy Group Specialized Register, 20 from the South Asian Database of Controlled Clinical Trials, and one from ClinicalTrials.gov. The search of IndMED yielded no references). After de-duplication, 24 references remained. After further scrutiny, only one study was identified for inclusion in this review.

Figure 2 shows the results of our searches.

Figure 2.

Study flow diagram.

Included studies

Only one study was included in the review (Rossetti 2011). The overview of the study is given in Table 1.

Excluded studies

None.

Risk of bias in included studies

The study conducted by Rossetti et al (Rossetti 2011) was a single-blind study. The small sample size and lack of double blinding could have influenced results.

Allocation

It is difficult to understand how allocation was done, as the authors have not commented on this in their paper. Personal communication with the author failed to clarify this issue.

Blinding

This was a single-blind study and so there is definitely a chance of performance bias and detection bias.

Incomplete outcome data

Attrition bias is unlikely, as there are no incomplete outcome data.

Selective reporting

Reporting bias is unlikely as the authors have reported all the outcomes they have described in the methodology.

Other potential sources of bias

No other potential sources of bias could be identified.

Effects of interventions

The initial search in May 2011 identified no results. Searching other databases in July 2011, we identified only one study (Rossetti 2011) that met our inclusion criteria. This was a randomised, single-blind study that included patients with RSE treated with either propofol or barbiturates. The details of the study have been outlined above.

Total control of seizures

There was no statistical difference in total control of seizures after the first course of study drug between propofol and thiopental sodium; 6/14 patients versus 2/7 patients in propofol and thiopental sodium group, respectively (RR 1.50; 95% CI 0.40 to 5.61) (Analysis 1.1).

Mortality

There was no statistical difference in mortality between propofol and thiopental sodium; 3/14 patients versus 1/7 patients in propofol and thiopental sodium group, respectively (RR 1.50; 95% CI 0.19 to 11.93). In the propofol group, deaths presumed to be in-hospital were secondary to Creuzfeldt-Jakob disease (day five), cardiac asystole (day six) and progressive brain tumour (day 11). In the thiopental group, one patient died on day five, secondary to colic ischaemia. Deaths on days 21, 29 and 42 were due to paraneoplastic encephalitis, pneumonia and sepsis, respectively, which are presumed to be out-of-hospital (Analysis 1.2).

Adverse events

There was no statistical difference in adverse events between propofol and thiopental sodium (Table 2). Infection was seen in 7/14 patients versus 5/7 patients in propofol and thiopental sodium group, respectively (RR 0.70; 95% CI 0.35 to 1.41).

Hypotension during administration of study drugs and requiring use of vasopressors was seen in 7/14 patients versus 4/7 patients in propofol and thiopental sodium group, respectively (RR 0.87; 95% CI 0.38 to 2.00) (Analysis 1.3).

The other severe complication noted was non-fatal propofol infusion syndrome in one patient.

Duration of mechanical ventilation

The number of days of mechanical ventilation were more in the thiopental group when compared with propofol group (median (range): 17 days (5 to 70 days) with thiopental sodium versus 4 days (2 to 28 days) with propofol).

Long-term outcome

There was no statistical difference in the functional outcome between propofol and thiopental sodium at three months; 5/14 patients versus 3/7 patients in propofol and thiopental sodium group, respectively (RR 0.83; 95% CI 0.28 to 2.52) (Analysis 1.4).

Discussion

Our search identified only one study (Rossetti 2011) that addressed the issue of treatment of RSE using thiopental sodium and propofol in a randomised, single-blind multicentric trial. This trial was under-sampled and had to be terminated prior to completion. Twenty-four patients were recruited in five centres; 14 received propofol and seven received thiopental sodium. The primary end point, that is, control of seizure with first course of drug treatment, was achieved in 43% in the propofol group and 22% in the barbiturate group (seven patients received thiopental sodium and two patients received pentobarbital). The overall mortality was 43% and 34% in the propofol and barbiturate group, respectively. However, the authors fail to report the in-hospital mortality. Patients returning to baseline condition at the three months' follow-up were similar in the two groups. No information was provided on the length of intensive care unit (ICU) and hospital days of the patients. However, days of mechanical ventilation were significantly more in the thiopental group. This could be due to the long elimination half-life of the drug when compared with propofol. The fact that the trial was prematurely stopped could have introduced bias. At the same time, the under-sampling resulted in loss of power to detect difference between the two treatment arms.

This study confirms that RSE is a serious clinical condition carrying high morbidity and mortality. The authors of the study agree that a larger multicentric study is needed with larger sample size and adequate funding is needed to reach conclusive results. The authors also suggest that a third treatment arm using midazolam as the treatment drug may be included in the study that may address the issue related to tolerability of the drugs, propofol and thiopental.

Summary of main results

Both propofol and thiopental sodium are broadly comparable in terms of seizure control, mortality, rate of complications and long-term outcome of patients with RSE. The 95% confidence interval was wide and allowed for a up to a more than two-fold difference between the two drugs. Days of mechanical ventilation were more in patients receiving thiopental sodium when compared with propofol.

Overall completeness and applicability of evidence

There is lack of evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. We are unable to detect a difference between the two drugs due to methodological issues. There is a need for a large, randomised controlled trial for this serious condition.

Quality of the evidence

Low.

Potential biases in the review process

None known.

Agreements and disagreements with other studies or reviews

To date this is the only eligible study available.

Authors' conclusions

Implications for practice

There are no data from randomised controlled trials that can clarify the superiority of thiopental sodium and propofol over each other in the treatment of RSE. Clinicians managing such cases of RSE should be aware of the adverse effects of the two anaesthetics drugs.

Implications for research

RSE is a serious clinical condition where conducting clinical trials may be difficult. Various ethical and methodological issues may arise. However, the problem itself is important and needs to be resolved. Use of thiopental sodium and propofol in RSE patients should be assessed with good-quality multicentric, randomised controlled trials, for their effect and efficacy in terms of total control of seizures, mortality, length of ICU and hospital stay, adverse effects and long-term outcome, such as dependence for daily activities. Many centres may have to be involved to enrol a suitable number of patients so that adequate power of the study can be achieved. A standard method may have to be followed with uniform outcome measures.

Acknowledgements

We wish to thank The Cochrane Epilepsy Group for their continuous support in helping us prepare the protocol. We would like to thank Professor A Rossetti for providing the additional data and information on the included study. We wish to thank the South Asian Cochrane Network and Centre, CMC, Vellore, India, who conducted the workshop at the Prof. BV Moses and ICMR Center for Advanced Research and Training in Evidence-Informed Healthcare, where this review was completed.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Rossetti 2011

  1. EEG: electroencephalography; iv: intravenous; RSE: refractory status epilepticus.

Methods

Pragmatic randomised controlled trial, single-blind, multicentric trial

Participants

Participants: adults (> 16 years) with RSE not due to cerebral anoxia, who clinically required coma

Sex (female/male): propofol group: 50%/50%; barbiturate group: 66%/34%

Age (median [range]): propofol group: 57 years (26 to 87 years); barbiturate group: 64 years (16 to 78 years)

Ethnic groups: not reported

Duration of epilepsy: not reported

Inclusion criteria: patients > 16 years of age suffering from RSE receiving at least 1 first-line and 1 second-line drug in adequate doses

Exclusion criteria: patients with known pregnancy, known intolerance to the study drugs, mitochondrial disorders, egg allergy, hypertriglyceridaemia (> 5 mmol/L) or significant rhabdomyolysis (creatinine kinase > 1500 U/L) on admission

Diagnostic criteria: RSE not due to cerebral anoxia, defined as ongoing clinical or electrographic seizures, or repetitive seizures without return to baseline for at least 30 minutes despite administration of 1 first-line (benzodiazepine) and 1 second-line antiepileptic drug (phenytoin, valproate, phenobarbital and levetiracetam) in adequate doses

Comorbidities: none

Co-medications: none

Total randomised: 24 patients; 14 allocated to propofol group and 10 allocated to barbiturate group; (1 patient in thiopental sodium group did not require treatment and so excluded, remaining 9 analysed)

Interventions

Number of control centre: 2

Country/location: Switzerland and US

Setting: CHUV et Universite de Lausanne, Lausanne and Brigham and Women's Hospital, Harvard School of Medicaine, Boston

Intervention I: 2 mg/kg titrated to burst suppression or 4 mg/kg until EEG was available

Intervention II: 2 mg/kg iv titrated to burst suppression or 5 mg/kg if no EEG available

Treatment before study: first- and second-line antiepileptic drugs

Time to treatment since onset of status: not reported

Duration of follow-up: 3 months

2 treatment arms: propofol and barbiturates (thiopental sodium or pentobarbital)

Outcomes

Primary outcomes (as stated in the publication): to assess the effectiveness (RSE control, adverse events) of a first course of propofol versus barbiturates

Secondary outcomes (as stated in the publication): none

Additional outcomes

Outcome used in our review:

  • total control of seizures

  • mortality

  • adverse events

  • duration of mechanical ventilation

  • functional outcome

Notes

Stated aim of study: "This prospective study was undertaken to assess the effectiveness (SE control, adverse events) of a first course of PRO versus barbiturates, the two most commonly used agents according to the aforementioned surveys"

Language of publication: English

Commercial funding: yes

Non-commercial funding: no

Publication status(peer review journal): yes

Publication status (journal supplement): no

Publication status (abstract): no

Funded by AstraZeneca (Switzerland) and UCB (Switzerland)

No conflict of interest

Clinical Trial.gov ID: NCT00265616

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"After written consent was obtained by proxy, randomisation was stratified by institution using sealed envelopes"

Comment: probably done

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Comment: authors contacted. No information provided

Blinding (performance bias and detection bias)

Subjective Outcomes

High risk

Being a single-blind study, only the patient was blinded. Assessors were not blinded

Incomplete outcome data (attrition bias)

All outcomes

Low risk

No loss to follow-up. All participants randomised completed the study and were included in final analysis

Selective reporting (reporting bias)

Low risk

All outcomes that were mentioned in the methodology have been reported

Other bias

Unclear risk

Trial was terminated before completion due to inadequate recruitment

Funding by pharmaceutical companies

Data and analyses

Download statistical data

Table Comparison 1. Propofol versus thiopental sodium
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

1 Total control of seizures

121Risk Ratio (M-H, Fixed, 95% CI)1.5 [0.40, 5.61]

2 Mortality

121Risk Ratio (M-H, Fixed, 95% CI)1.5 [0.19, 11.93]

3 Adverse events

1 Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

  3.1 Infection

121Risk Ratio (M-H, Fixed, 95% CI)0.70 [0.35, 1.41]

  3.2 Hypotension

121Risk Ratio (M-H, Fixed, 95% CI)0.87 [0.38, 2.00]

  3.3 Other serious complication

121Risk Ratio (M-H, Fixed, 95% CI)0.5 [0.04, 6.86]

4 Long-term outcome

121Risk Ratio (M-H, Fixed, 95% CI)0.83 [0.28, 2.52]

5 Duration of mechanical ventilation

  Other dataNo numeric data
Figure Analysis 1.1.

Comparison 1 Propofol versus thiopental sodium, Outcome 1 Total control of seizures.

Figure Analysis 1.2.

Comparison 1 Propofol versus thiopental sodium, Outcome 2 Mortality.

Figure Analysis 1.3.

Comparison 1 Propofol versus thiopental sodium, Outcome 3 Adverse events.

Figure Analysis 1.4.

Comparison 1 Propofol versus thiopental sodium, Outcome 4 Long-term outcome.

Figure Analysis 1.5.

Comparison 1 Propofol versus thiopental sodium, Outcome 5 Duration of mechanical ventilation.

Additional Tables

Table 1. Overview of study populations
  1. I1: intervention 1; I2: intervention 2; ITT: intention to treat; n: number.

Study IDInterventionsScreened (n)Randomised (n)Safety analysis (n)ITT (n)Finishing study (n)[%] of randomised participants finishing study
Rossetti 2011

I1 Propofol

I2 Barbiturate

I1 14

I2 10

I1 14

I2 10

I1 14

I2 10

I1 14

I2 10

I1 14

I2 9

I1 100

I2 90

Table 2. Adverse effects
  1. I1: intervention 1; I2: intervention 2; ICU: intensive care unit; n: number.

CharacteristicRossetti 2011

I1

I2

Propofol

Thiopental

Participants who died (n)

Epilepsy-related

I1 Propofol

I2 Thiopental

0

0

Participants who died (n)

All causes

I1 Propofol

I2 Thiopental

3

1

Adverse events (n)

I1 Propofol

I2 Thiopental

14

11

Serious adverse events (n)

I1 Propofol

I2 Thiopental

1

1

Duration of ICU stayNot reported

Duration of mechanical ventilation (median (range))

I1 Propofol

I2 Thiopental

17 days (5 to 70 days)

4 days (2 to 28 days)

Duration of hospitalisationNot reported
Neurological deficitsNot reported
Cognitive deficitsNot reported
Haematological toxicityNot reported
Liver toxicityNot reported
Hypersensitivity or drug allergyNot reported
BronchopneumoniaNot reported
Other side effectsNot reported

Appendices

Appendix 1. CENTRAL search strategy

#1 status epilepticus

#2 MeSH descriptor Status Epilepticus explode all trees

#3 (thiopental) or (thiopentone)

#4 MeSH descriptor Barbiturates explode all trees

#5 MeSH descriptor Thiopental explode all trees

#6 (#3 OR #4 OR #5)

#7 MeSH descriptor Propofol explode all trees

#8 (propofol)

#9 (#7 OR #8)

#10 (#1 OR #2)

#11 (#6 AND #9 AND #10)

Appendix 2. MEDLINE search strategy

This strategy is based on the Cochrane Highly Sensitive Search Strategy for identifying randomised trials published in Lefebvre 2009.

1. randomized controlled trial.pt.

2. controlled clinical trial.pt.

3. randomized.ab.

4. placebo.ab.

5. clinical trials as topic.sh.

6. randomly.ab.

7. trial.ti.

8. 7 or 5 or 2 or 6 or 1 or 4 or 3

9. exp animals/ not humans.sh.

10. 8 not 9

11. exp Status Epilepticus/

12. status epilepticus.tw.

13. 11 or 12

14. exp Thiopental/

15. exp Barbiturates/

16. (thiopental or thiopentone).tw.

17. 14 or 15 or 16

18. exp Propofol/

19. propofol.tw.

20. 18 or 19

21. 17 and 20

22. 10 and 13 and 21

History

Protocol first published: Issue 7, 2011

Review first published: Issue 8, 2012

Contributions of authors

Conceiving the review: Hemanshu Prabhakar (HP)

Co-ordinating the review: HP

Undertaking manual searches: HP, Ashish Bindra (AB)

Screening search results: HP, Gyaninder Pal Singh (GPS)

Organising retrieval of papers: HP, AB

Screening retrieved papers against inclusion criteria: HP, GPS

Appraising quality of papers: HP, GPS

Extracting data from papers: HP, GPS

Writing to authors of papers for additional information: HP, AB

Providing additional data about papers: HP, AB

Obtaining and screening data on unpublished studies: HP, AB

Data management for the review: HP, Mani Kalaivani (MK)

Entering data into Review Manager (RevMan 2011): HP

RevMan statistical data: HP, MK

Other statistical analysis not using RevMan: HP, MK

Double entry of data: (data entered by person one: HP; data entered by person two: GPS)

Interpretation of data: HP, MK

Statistical inferences: HP, MK

Writing the review: HP, AB

Guarantor for the review (one author): HP

Person responsible for reading and checking review before submission: HP, AB, MK

Declarations of interest

None known.

Sources of support

Internal sources

  • All India Institute of Medical Sciences, New Delhi, India.

External sources

  • No sources of support supplied

Differences between protocol and review

The primary outcome in our protocol 'total control of seizures' is defined as total control of seizures after the first course of the study drug.

By 'mortality' we meant only the in-hospital mortality of the patients receiving study drugs. It does not include deaths after the patients were discharged from the hospital.

A Google Scholar database search has not been conducted and so it has been removed from the list.

Ancillary