Mannitol for acute traumatic brain injury.

BACKGROUND: Mannitol is sometimes effective in reversing acute brain swelling, but its effectiveness in the ongoing management of severe head injury remains unclear. There is evidence that, in prolonged dosage, mannitol may pass from the blood into the brain, where it might cause increased intracranial pressure. OBJECTIVES: To assess the effects of different mannitol therapy regimens, of mannitol compared to other intracranial pressure (ICP) lowering agents, and to quantify the effectiveness of mannitol administration given at other stages following acute traumatic brain injury. SEARCH STRATEGY: The review drew on the search strategy for the Injuries Group as a whole. We checked reference lists of trials and review articles, and contacted authors of trials. The searches were last updated in March 2006. SELECTION CRITERIA: Randomised controlled trials of mannitol, in patients with acute traumatic brain injury of any severity. The comparison group could be placebo-controlled, no drug, different dose, or different drug. We excluded cross-over trials, and trials where the intervention was started more than eight weeks after injury. DATA COLLECTION AND ANALYSIS: We independently rated quality of allocation concealment and extracted the data. Relative risks (RR) and 95% confidence intervals (CI) were calculated for each trial on an intention to treat basis. MAIN RESULTS: We identified four eligible randomised controlled trials. One trial compared ICP-directed therapy to 'standard care' (RR for death = 0.83; 95% CI 0.47 to 1.46). One trial compared mannitol to pentobarbital (RR for death = 0.85; 95% CI 0.52 to 1.38). One trial compared mannitol to hypertonic saline (RR for death = 1.25; 95% CI 0.47 to 3.33). One trial tested the effectiveness of pre-hospital administration of mannitol against placebo (RR for death = 1.75; 95% CI 0.48 to 6.38). AUTHORS' CONCLUSIONS: Mannitol therapy for raised ICP may have a beneficial effect on mortality when compared to pentobarbital treatment, but may have a detrimental effect on mortality when compared to hypertonic saline. ICP-directed treatment shows a small beneficial effect compared to treatment directed by neurological signs and physiological indicators. There are insufficient data on the effectiveness of pre-hospital administration of mannitol.

Mannitol for acute traumatic brain injury.

BACKGROUND: Mannitol is sometimes effective in reversing acute brain swelling, but its effectiveness in the ongoing management of severe head injury remains unclear. There is evidence that, in prolonged dosage, mannitol may pass from the blood into the brain, where it might cause increased intracranial pressure. OBJECTIVES: To assess the effects of different mannitol therapy regimens, of mannitol compared to other intracranial pressure (ICP) lowering agents, and to quantify the effectiveness of mannitol administration given at other stages following acute traumatic brain injury. SEARCH STRATEGY: The review drew on the search strategy for the Injuries Group as a whole. We checked reference lists of trials and review articles, and contacted authors of trials. The searches were last updated in April 2005. SELECTION CRITERIA: Randomised trials of mannitol, in patients with acute traumatic brain injury of any severity. The comparison group could be placebo-controlled, no drug, different dose, or different drug. We excluded cross-over trials, and trials where the intervention was started more than eight weeks after injury. DATA COLLECTION AND ANALYSIS: The reviewers independently rated quality of allocation concealment and extracted the data. Relative risks (RR) and 95% confidence intervals (CI) were calculated for each trial on an intention to treat basis. MAIN RESULTS: In the acute management of comatose patients with severe head injury, the administration of high-dose mannitol resulted in reduced mortality (RR= 0.56; 95% CI 0.39 to 0.79) and reduced death and severe disability (RR= 0.58; 95% CI 0.47 to 0.72) when compared with conventional-dose mannitol. One trial compared ICP-directed therapy to 'standard care' (RR for death= 0.83; 95% CI 0.47 to 1.46). One trial compared mannitol to pentobarbital (RR for death= 0.85; 95% CI 0.52 to 1.38). One trial compared mannitol to hypertonic saline (RR for death= 1.25; 95% CI 0.47 to 3.33). One trial tested the effectiveness of pre-hospital administration of mannitol against placebo (RR for death= 1.75; 95% CI 0.48 to 6.38). AUTHORS' CONCLUSIONS: High-dose mannitol may be preferable to conventional-dose mannitol in the acute management of comatose patients with severe head injury. Mannitol therapy for raised ICP may have a beneficial effect on mortality when compared to pentobarbital treatment, but may have a detrimental effect on mortality when compared to hypertonic saline. ICP-directed treatment shows a small beneficial effect compared to treatment directed by neurological signs and physiological indicators. There are insufficient data on the effectiveness of pre-hospital administration of mannitol.

Colloids versus crystalloids for fluid resuscitation in critically ill patients.

BACKGROUND: Colloid solutions are widely used in fluid resuscitation of critically ill patients. There are several choices of colloid and there is ongoing debate about the relative effectiveness of colloids compared to crystalloid fluids. OBJECTIVES: To assess the effects on mortality of colloids compared to crystalloids for fluid resuscitation in critically ill patients. SEARCH STRATEGY: We searched the Injuries Group specialised register, Cochrane Controlled Trials Register, MEDLINE, EMBASE and BIDS Index to Scientific and Technical Proceedings, and checked reference lists of trials and review articles. SELECTION CRITERIA: All randomised and quasi-randomised trials of colloids compared to crystalloids, in patients requiring volume replacement. Cross-over trials and trials in pregnant women and neonates were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and rated quality of allocation concealment. Trials with a 'double-intervention', such as those comparing colloid in hypertonic crystalloid to isotonic crystalloid, were analysed separately. The analysis was stratified according to colloid type and quality of allocation concealment. MAIN RESULTS: Colloids compared to crystalloidsAlbumin or plasma protein fraction. Nineteen trials reported data on mortality, including a total of 7576 patients. The pooled relative risk (RR) from these trials was 1.02 (95% confidence interval [95% CI] 0.93 to 1.11). When the trial with poor quality allocation concealment was excluded, pooled RR was 1.01 (95% CI 0.92 to 1.10). Hydroxyethyl starch. Ten trials compared hydroxyethyl starch with crystalloids, including a total of 374 randomised participants. The pooled RR was 1.16 (95% CI 0.68 to 1.96). Modified gelatin. Seven trials compared modified gelatin with crystalloid, including a total of 346 randomised participants. The pooled RR was 0.54 (95% CI 0.16 to 1.85). Dextran. Nine trials compared dextran with a crystalloid, including a total of 834 randomised participants. The pooled relative risk was RR 1.24 (95% CI 0.94 to 1.65). Colloids in hypertonic crystalloid compared to isotonic crystalloidEight trials compared dextran in hypertonic crystalloid with isotonic crystalloid, including 1283 randomised participants. Pooled RR was 0.88 (95% CI 0.74 to 1.05). REVIEWERS' CONCLUSIONS: There is no evidence from randomised controlled trials that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids, in patients with trauma, burns or following surgery. As colloids are not associated with an improvement in survival, and as they are more expensive than crystalloids, it is hard to see how their continued use in these patients can be justified outside the context of randomised controlled trials.

Human albumin solution for resuscitation and volume expansion in critically ill patients.

BACKGROUND: Human albumin solutions are used in a range of medical and surgical problems. Licensed indications are the emergency treatment of shock and other conditions where restoration of blood volume is urgent, burns, and hypoproteinaemia. Human albumin solutions are more expensive than other colloids and crystalloids. OBJECTIVES: To quantify the effect on mortality of human albumin and plasma protein fraction (PPF) administration in the management of critically ill patients. SEARCH STRATEGY: We searched the Cochrane Injuries Group trials register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and BIDS Index to Scientific and Technical Proceedings. Reference lists of trials and review articles were checked, and authors of identified trials were contacted. The search was last updated in August 2004. SELECTION CRITERIA: Randomised controlled trials comparing albumin/PPF with no albumin/PPF, or with a crystalloid solution, in critically ill patients with hypovolaemia, burns or hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the participants, albumin solution used, mortality at the end of follow up, and quality of allocation concealment. Analysis was stratified according to patient type. MAIN RESULTS: We found 32 trials meeting the inclusion criteria and reporting death as an outcome. There were 1632 deaths among 8452 trial participants. For hypovolaemia, the relative risk of death following albumin administration was 1.01 (95% confidence interval 0.92, 1.10). This estimate was heavily influenced by the results of the SAFE trial which contributed 91% of the information (based on the weights in the meta-analysis). For burns, the relative risk was 2.40 (1.11, 5.19) and for hypoalbuminaemia the relative risk was 1.38 (0.94, 2.03). There was no substantial heterogeneity between the trials in the various categories (chi-square = 21.86, df = 25, p =0.64). The pooled relative risk of death with albumin administration was 1.04 (0.95, 1.13). REVIEWERS' CONCLUSIONS: For patients with hypovolaemia there is no evidence that albumin reduces mortality when compared with cheaper alternatives such as saline. There is no evidence that albumin reduces mortality in critically ill patients with burns and hypoalbuminaemia. The possibility that there may be highly selected populations of critically ill patients in which albumin may be indicated remains open to question. However, in view of the absence of evidence of a mortality benefit from albumin and the increased cost of albumin compared to alternatives such as saline, it would seem reasonable that albumin should only be used within the context of well concealed and adequately powered randomised controlled trial.

Mannitol for acute traumatic brain injury.

BACKGROUND: Mannitol is sometimes dramatically effective in reversing acute brain swelling, but its effectiveness in the on-going management of severe head injury remains open to question. There is evidence that, in prolonged dosage, mannitol may pass from the blood into the brain, where it might cause reverse osmotic shifts that increase intracranial pressure. OBJECTIVES: To assess the effects of different mannitol therapy regimens, of mannitol compared to other intracranial pressure (ICP) lowering agents, and to quantify the effectiveness of mannitol administration given at other stages following acute traumatic brain injury. SEARCH STRATEGY: The review drew on the search strategy for the Injuries Group as a whole. We checked reference lists of trials and review articles, and contacted authors of trials. SELECTION CRITERIA: Randomised trials of mannitol, in patients with acute traumatic brain injury of any severity. The comparison group could be placebo-controlled, no drug, different dose, or different drug. Trials where the intervention was started more than eight weeks after injury, and cross-over trials were excluded. DATA COLLECTION AND ANALYSIS: The reviewers independently rated quality of allocation concealment and extracted the data. Relative risks (RR) and 95% confidence intervals (CI) were calculated for each trial on an intention to treat basis. MAIN RESULTS: Overall there were few eligible trials. In the pre-operative management of patients with acute intracranial haemorrhage the administration of high-dose mannitol resulted in reduced mortality (RR=0.55; 95%CI 0.36, 0.84) and reduced death and severe disability (RR=0.58; 95%CI 0.45, 0.74) when compared with conventional-dose mannitol. One trial compared ICP-directed therapy to 'standard care' (RR for death= 0.83; 95%CI 0.47,1.46). One trial compared mannitol to pentobarbital (RR for death = 0.85; 95% CI 0.52, 1.38). No trials compared mannitol to other ICP-lowering agents. One trial tested the effectiveness of pre-hospital administration of mannitol against placebo (RR for death=1.75; 95% CI 0.48, 6.38). REVIEWER'S CONCLUSIONS: High-dose mannitol appears to be preferable to conventional-dose mannitol in the pre-operative management of patients with acute intracranial haematomas. However, there is little evidence about the use of mannitol as a continuous infusion in patients with raised intracranial pressure in patients who do not have an operable intracranial haematoma. Mannitol therapy for raised ICP may have a beneficial effect on mortality when compared to pentobarbital treatment. ICP-directed treatment shows a small beneficial effect compared to treatment directed by neurological signs and physiological indicators. There are insufficient data on the effectiveness of pre-hospital administration of mannitol to preclude either a harmful or a beneficial effect on mortality.

Human albumin solution for resuscitation and volume expansion in critically ill patients.

BACKGROUND: Human albumin solutions are used in a range of medical and surgical problems. Licensed indications are the emergency treatment of shock and other conditions where restoration of blood volume is urgent, burns, and hypoproteinaemia. Human albumin solutions are more expensive than other colloids and crystalloids. OBJECTIVES: To quantify the effect on mortality of human albumin and plasma protein fraction (PPF) administration in the management of critically ill patients. SEARCH STRATEGY: We searched the Cochrane Injuries Group trials register, Cochrane Controlled Trials Register, Medline, Embase and BIDS Index to Scientific and Technical Proceedings. Reference lists of trials and review articles were checked, and authors of identified trials were contacted. The search was last updated in November 2001. SELECTION CRITERIA: Randomised controlled trials comparing albumin/PPF with no albumin/PPF, or with a crystalloid solution, in critically ill patients with hypovolaemia, burns or hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the participants, albumin solution used, mortality at the end of follow up, and quality of allocation concealment. Analysis was stratified according to patient type. MAIN RESULTS: We found 31 trials meeting the inclusion criteria and reporting death as an outcome. There were 177 deaths among 1519 trial participants. For each patient category the risk of death in the albumin treated group was higher than in the comparison group. For hypovolaemia the relative risk of death following albumin administration was 1.46 (95% confidence interval 0.97 to 2.22), for burns the relative risk was 2.40 (1.11 to 5.19), and for hypoalbuminaemia the relative risk was 1.38 (0.94 to 2.03). The pooled relative risk of death with albumin administration was 1.52 (1.17 to 1.99). Overall, the risk of death in patients receiving albumin was 14% compared to 9% in the control groups, an increase in the risk of death of 5% (2% to 8%). These data suggest that for every 20 critically ill patients treated with albumin there is one additional death. REVIEWER'S CONCLUSIONS: There is no evidence that albumin administration reduces the risk of death in critically ill patients with hypovolaemia, burns or hypoalbuminaemia, and a strong suggestion that it may increase the risk of death. These data suggest that the use of human albumin in critically ill patients should be urgently reviewed and that it should not be used outside the context of a rigorously conducted randomised controlled trial.

Anti-epileptic drugs for preventing seizures following acute traumatic brain injury.

BACKGROUND: Seizure activity in the early post-traumatic period following head injury may cause secondary brain damage as a result of increased metabolic demands, raised intracranial pressure and excess neurotransmitter release. OBJECTIVES: To determine the effects of prophylactic anti-epileptic agents for acute traumatic head injury. SEARCH STRATEGY: We searched the Cochrane Injuries Group specialised register, Medline and the registers of the Cochrane Stroke Group and Cochrane Epilepsy Group. We contacted pharmaceutical companies who manufacture anti-epileptic agents, the National Institute of Neurological Disorders and Stroke, Epilepsy Division, and the National Institute of Health, United States. SELECTION CRITERIA: All randomised trials of anti-epileptic agents, in which study participants had a clinically defined acute traumatic head injury of any severity. Trials in which the intervention was started more than eight weeks after injury were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed the trial quality. Relative risks and 95% confidence intervals were calculated for each trial on an intention to treat basis, which included pre-drug loading exclusions. As long as statistical heterogeneity did not exist, for dichotomous data, summary relative risks and 95% confidence intervals were calculated using a fixed effects model. Where the source of heterogeneity could obviously be related to allocation concealment, drug type, or drug dose, we stratified the analyses on that dimension. MAIN RESULTS: We identified 10 eligible randomised controlled trials, including 2036 participants, but data was unavailable for four unpublished trials, representing 631 participants and they were excluded. For the remaining six trials, the pooled relative risk (RR) for early seizure prevention was 0.34 (95% confidence interval 0.21 to 0.54); based on this estimate, for every 100 patients treated, 10 would be kept seizure free in the first week. Seizure control in the acute phase was not accompanied by a reduction in mortality (RR=1.15; 95% confidence interval 0.89 to 1.51), a reduction in death and neurological disability (RR = 1.49; 95% confidence interval 1.06 to 2.08 for carbamazepine and RR= 0.96; 95% confidence interval 0.72 to 1.26 for phenytoin) or a reduction in late seizures (pooled RR =1.28; 95% confidence interval 0.90 to 1.81). The pooled relative risk for skin rashes was 1.57 (95% confidence interval 0.57 to 39.88). REVIEWER'S CONCLUSIONS: Prophylactic anti-epileptics are effective in reducing early seizures, but there is no evidence that treatment with prophylactic anti-epileptics reduces the occurrence of late seizures, or has any effect on death and neurological disability. Insufficient evidence is available to establish the net benefit of prophylactic treatment at any time after injury.

Predictors of low back pain onset in a prospective British study.

OBJECTIVES: This study examined predictors of low back pain onset in a British birth cohort. METHODS: Univariate and multivariate analyses focused on individuals who experienced onset of low back pain at 32 to 33 years of age (n= 571) and individuals who were pain free (n = 5210). Participants were members of the 1958 British birth cohort. RESULTS: Incident pain was elevated among those with psychological distress at 23 years of age (adjusted odds ratio [OR] = 2.52, 95% confidence interval [CI] = 1.65, 3.86) and among persistent moderate or heavy smokers (adjusted OR = 1.63, 95% CI = 1.23, 2.17). Significant univariate associations involving other factors (e.g., social class, childhood emotional status, body mass index, job satisfaction) did not persist in multivariate analyses. CONCLUSIONS: This prospectively studied cohort provides evidence that psychological distress more than doubles later risk of low back pain, with smoking having a modest independent effect. Other prospective studies are needed to confirm these findings before implications for low back pain prevention can be assessed.

Anti-epileptic drugs for preventing seizures following acute traumatic brain injury.

BACKGROUND: Seizure activity in the early post-traumatic period following head injury may cause secondary brain damage as a result of increased metabolic demands, raised intracranial pressure and excess neurotransmitter release. OBJECTIVES: To determine the effects of prophylactic anti-epileptic agents for acute traumatic head injury. SEARCH STRATEGY: We searched the Cochrane Injuries Group trials register, Medline and the databases of the Cochrane Stroke Group and Cochrane Epilepsy Group. We also contacted pharmaceutical companies who manufacture anti-epileptic agents, the National Institute of Neurological Disorders and Stroke, Epilepsy Division, and the National Institute of Health, United States. SELECTION CRITERIA: All randomised trials of anti-epileptic agents, in which study participants had a clinically defined acute traumatic head injury of any severity. Trials in which the intervention was started more than eight weeks after injury were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed the quality of the trials. Relative risks and 95% confidence intervals were calculated for each trial on an intention to treat basis, which included pre-drug loading exclusions. As long as statistical heterogeneity did not exist, for dichotomous data, summary relative risks and 95% confidence intervals were calculated using a fixed effects model. Where the source of heterogeneity could obviously be related to allocation concealment, drug type, or drug dose, we stratified the analyses on that dimension. MAIN RESULTS: We identified 10 eligible randomised controlled trials, including 2036 participants. Data are currently unavailable for four unpublished trials, representing 631 participants. For the remaining trials, the pooled relative risk (RR) for early seizure prevention was 0.34 (95% confidence interval 0.21 to 0.54); based on this estimate, for every 100 patients treated, 10 would be kept seizure free in the first week. Seizure control in the acute phase was not accompanied by a reduction in mortality (RR=1.15; 95% confidence interval 0.89 to 1. 51), a reduction in death and neurological disability (RR = 1.49; 95% confidence interval 1.06 to 2.08 for carbamazepine and RR= 0.96; 95% confidence interval 0.72 to 1.26 for phenytoin) or a reduction in late seizures (pooled RR =1.28; 95% confidence interval 0.90 to 1. 81). The pooled relative risk for skin rashes was 1.57 (95% confidence interval 0.57 to 39.88). REVIEWER'S CONCLUSIONS: Prophylactic anti-epileptics are effective in reducing early seizures, but there is no evidence that treatment with prophylactic anti-epileptics reduces the occurrence of late seizures, or has any effect on death and neurological disability. Insufficient evidence is available to establish the net benefit of prophylactic treatment at any time after injury.

Hyperventilation therapy for acute traumatic brain injury.

BACKGROUND: Because hyperventilation is often associated with a rapid fall in intracranial pressure, it has been assumed to be effective in the treatment of severe head injury. Hyperventilation reduces raised intracranial pressure by causing cerebral vasoconstriction and a reduction in cerebral blood flow. Whether reduced cerebral blood flow improves neurological outcome however, is unclear. OBJECTIVES: To quantify the effect of hyperventilation on death and neurological disability following head injury. SEARCH STRATEGY: The search strategy drew on that of the Injuries Group as a whole. The reference lists of all relevant articles identified were checked and the first author of reports was contacted to ask for assistance in identifying any further trials. Most recent search was done in September 1999. SELECTION CRITERIA: All randomised trials of hyperventilation, in which study participants had a clinically defined acute traumatic head injury of any severity. There were no language restrictions. DATA COLLECTION AND ANALYSIS: We collected data on the participants, the timing and duration of the intervention, duration of follow up, neurological disability and death. Relative risks (RR) and 95% confidence intervals were calculated for each trial on an intention to treat basis. Timing, degree and duration of hyperventilation were identified a-priori as potential sources of heterogeneity between trials. MAIN RESULTS: One trial of 113 participants was identified. Hyperventilation alone, as well as in conjunction with the buffer THAM showed a beneficial effect on mortality at one year after injury, although the effect measure was imprecise (RR=0.73; 95% CI 0.36;1.49 and RR=0.89; 95% CI 0.47;1.72 respectively). This improvement in outcome was not supported by an improvement in neurological recovery. For hyperventilation alone, the RR for death or severe disability was 1. 14 (95% CI 0.82;1.58). The RR for death or severe disability in the hyperventilation plus THAM group, was 0.87 (95% CI 0.58;1.28). REVIEWER'S CONCLUSIONS: The data available are inadequate to assess any potential benefit or harm that might result from hyperventilation in severe head injury. Randomised controlled trials to assess the effectiveness of hyperventilation therapy following severe head injury are needed.

Colloids versus crystalloids for fluid resuscitation in critically ill patients.

BACKGROUND: Colloid solutions are widely used in fluid resuscitation of critically ill patients. There are several choices of colloid and there is ongoing debate about the relative effectiveness of colloids compared to crystalloid fluids. OBJECTIVES: To assess the effects on mortality of colloids compared to crystalloids for fluid resuscitation in critically ill patients. SEARCH STRATEGY: We searched the Injuries Group specialised register, Cochrane Controlled Trials Register, MEDLINE, EMBASE and BIDS Index to Scientific and Technical Proceedings and checked the reference lists of trials and review articles. SELECTION CRITERIA: All randomised and quasi-random trials of colloids compared to crystalloids, in patients requiring volume replacement. Cross-over trials and trials in pregnant women and neonates were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and rated quality of allocation concealment. Trials with a 'double-intervention' such as those, which compared colloid in hypertonic crystalloid to isotonic crystalloid, were analysed separately. The analysis was stratified according to colloid type and quality of allocation concealment. MAIN RESULTS: Colloids compared to crystalloids: Albumin or plasma protein fraction: Eighteen trials reported data on mortality, including a total of 641 patients. The pooled relative risk from these trials was 1.52 (95% confidence interval 1.08 to 2.13). The risk of death in the albumin treated group was 6% higher than in the crystalloid treated group (1% to 11%). When the trial with poor quality allocation concealment was excluded the pooled relative risk was 1.34 (0.95 to 1.89). Hydroxyethylstarch: Seven trials compared hydroxyethylstarch with crystalloids including a total of 197 randomised participants. The pooled relative risk was 1.16 (0.68 to 1.96). Modified gelatin: Four trials compared modified gelatin with crystalloid including a total of 95 randomised participants. The pooled relative risk was 0.50 (0. 08 to 3.03). Dextran: Eight trials compared dextran with a crystalloid including a total of 668 randomised participants. The pooled relative risk was 1.24 (0.94 to 1.65). Colloids in hypertonic crystalloid compared to isotonic crystalloid: Eight trials compared dextran in hypertonic crystalloid with isotonic crystalloid, including 1283 randomised participants. The pooled relative risk was 0.88 (0.74 to 1.05). REVIEWER'S CONCLUSIONS: There is no evidence from randomised controlled trials that resuscitation with colloids reduces the risk of death compared to crystalloids in patients with trauma, burns and following surgery. As colloids are not associated with an improvement in survival, and as they are more expensive than crystalloids, it is hard to see how their continued use in these patient types can be justified outside the context of randomised controlled trials.

Mannitol for acute traumatic brain injury.

BACKGROUND: Mannitol is sometimes dramatically effective in reversing acute brain swelling, but its effectiveness in the on-going management of severe head injury remains open to question. There is evidence that in prolonged dosage mannitol may pass from the blood into the brain, where it might cause reverse osmotic shifts that increase intracranial pressure. OBJECTIVES: To assess the effects of different mannitol therapy regimens, of mannitol compared to other intracranial pressure (ICP) lowering agents, and to quantify the effectiveness of mannitol administration given at other stages following acute traumatic brain injury. SEARCH STRATEGY: The review drew on the search strategy for the Injuries Group as a whole. We checked reference lists of trials and review articles, and contacted authors of trials. SELECTION CRITERIA: Randomised trials of mannitol, in patients with acute traumatic brain injury of any severity. The comparison group could be placebo-controlled, no drug, different dose, or different drug. Trials where the intervention was started more than eight weeks after injury, and cross-over trials were excluded. DATA COLLECTION AND ANALYSIS: The reviewers independently rated quality of allocation concealment and extracted the data. Relative risks (RR) and 95% confidence intervals (CI) were calculated for each trial on an intention to treat basis. MAIN RESULTS: Overall there were few eligible trials. There were no trials comparing different doses, or type of administration. One trial compared ICP-directed therapy to 'standard care' (RR for death= 0.83; 95% CI 0.47;1.46). One trial compared mannitol to pentobarbital (RR for death = 0.85; 95% CI 0. 52;1.38). No trials compared mannitol to other ICP lowering agents. One trial tested the effectiveness of pre-hospital administration of mannitol against placebo (RR for death=1.59; 95% CI 0.44;5.79). REVIEWER'S CONCLUSIONS: There are insufficient data to recommend one form of mannitol infusion over another. Mannitol therapy for raised ICP may have a beneficial effect on mortality when compared to pentobarbital treatment. ICP-directed treatment shows a small beneficial effect compared to treatment directed by neurological signs and physiological indicators. There are insufficient data on the effectiveness of pre-hospital administration of mannitol to preclude either a harmful or a beneficial effect on mortality.

Human albumin solution for resuscitation and volume expansion in critically ill patients. The Albumin Reviewers.

BACKGROUND: Human albumin solutions are used in a range of medical and surgical problems. Licensed indications are the emergency treatment of shock and other conditions where restoration of blood volume is urgent, burns, and hypoproteinaemia. Human albumin solutions are more expensive than other colloids and crystalloids. OBJECTIVES: To quantify the effect on mortality of human albumin and plasma protein fraction (PPF) administration in the management of critically ill patients. SEARCH STRATEGY: We searched the Cochrane Injuries Group trials register, Cochrane Controlled Trials Register, Medline, Embase and BIDS Index to Scientific and Technical Proceedings. Reference lists of trials and review articles were checked, and authors of identified trials were contacted. The search was last updated in November 1999. SELECTION CRITERIA: Randomised controlled trials comparing albumin/PPF with no albumin/PPF, or with a crystalloid solution, in critically ill patients with hypovolaemia, burns or hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the participants, albumin solution used, mortality at the end of follow up, and quality of allocation concealment. Analysis was stratified according to patient type. We assessed publication bias using the regression test for funnel plot asymmetry. MAIN RESULTS: We found 30 trials meeting the inclusion criteria and reporting death as an outcome. There were 156 deaths among 1419 trial participants. For each patient category the risk of death in the albumin treated group was higher than in the comparison group. For hypovolaemia the relative risk of death following albumin administration was 1.46 (95% confidence interval 0.97 to 2.22), for burns the relative risk was 2.40 (1.11 to 5.19), and for hypoalbuminaemia the relative risk was 1.69 (1.07 to 2.67). The pooled relative risk of death with albumin administration was 1.68 (1.26 to 2.23). Overall, the risk of death in patients receiving albumin was 14% compared to 8% in the control groups, an increase in the risk of death of 6% (3% to 9%). These data suggest that for every 17 critically ill patients treated with albumin there is one additional death. REVIEWER'S CONCLUSIONS: There is no evidence that albumin administration reduces the risk of death in critically ill patients with hypovolaemia, burns or hypoalbuminaemia, and a strong suggestion that it may increase the risk of death. These data suggest that the use of human albumin in critically ill patients should be urgently reviewed and that it should not be used outside the context of a rigorously conducted randomised controlled trial.

An assessment of care provided by a public sector STD clinic in Cape Town.

A study was undertaken in a Cape Town public sector STD clinic to evaluate the content and quality of care provided since it has been recognized that appropriate improvements in the management of conventional sexually transmitted diseases (STDs), including provision of correct therapy, health education, condom promotion and partner notification, could result in a reduced incidence of HIV infection. Our objectives were to assess patients' needs for health education and to assess the quality of STD management in terms of health education, condom promotion, partner notification, the validity of the clinical diagnoses and the adequacy of the treatments prescribed. The study subjects were sampled systematically, according to their gender. Patients included in the study were given a standardized interview and their clinical records reviewed. Specimens were collected for laboratory investigations. For each STD detected, the treatment was defined as adequate if drugs currently known to be active against that infection were prescribed. One hundred and seventy men and 161 women were included in the study (median age: females 22 years, males 26 years). While almost all patients believed their STD may have been caused by unprotected sexual intercourse, many also believed it may have been caused by other factors, such as bewitchment with traditional medicine. Only 21% of male and 37% of female patients received any education about STD transmission during the clinic visit, and only 25% of male and 36% of female patients received education about condom use. As a result of the low sensitivity of the clinicians' diagnoses, 16% of men and 61% of women left the clinic with at least one infection inadequately treated. The majority of patients were not receiving education for the prevention of STDs including HIV. Many were not receiving adequate treatment for their infections. The introduction of a syndromic management protocol in this setting would substantially reduce the proportion of inadequately-treated patients. However, syndromic protocols, and the means by which they are implemented, need to take into account problems with the clinical detection of genital ulcerative disease and candidiasis in women.

PIP: In South Africa's Western Cape Province, where sexually transmitted disease (STD) rates are high but HIV prevalence remains low, syndromic STD management in the public health services has been proposed as a strategy for curbing development of an AIDS epidemic. This study, conducted prior to the formal introduction of such a program, evaluated the quality of STD management at a local health authority clinic in Cape Town. 170 male and 161 female new clients presenting during the 6-week study period were enrolled. 76% of men and 81% of women reported they had never used a condom. Only 21% of male and 37% of female clients received health education concerning STD prevention during their visit. Contact slips to facilitate partner notification were provided to 28% of men and 25% of women. Condom use was discussed with just 25% of male and 36% of females. The most common clinical diagnosis made by staff was gonorrhea. According to the research physician's findings, 51 patients (40 men and 11 women) had genital ulcers, the majority of which were not detected by staff. Of 32 men and women diagnosed by staff clinicians as having no infections, 58% of men and 75% of women had at least 1 STD confirmed by laboratory testing. Overall, at least 16% of men and 61% of women left the clinic with 1 or more STD inadequately treated. These findings indicate that introduction of syndromic protocols in South Africa's public health services will not automatically improve STD diagnosis and treatment. Health education to correct misinformation about STDs, condom promotion and distribution, partner notification, and the validity of clinical diagnoses must be addressed.

Absence of evidence for the effectiveness of five interventions routinely used in the intensive care management of severe head injury: a systematic review.

OBJECTIVES: To assess the effectiveness of interventions routinely used in the intensive care management of severe head injury, specifically, the effectiveness of hyperventilation, mannitol, CSF drainage, barbiturates, and corticosteroids. METHODS: Systematic review of all unconfounded randomised trials, published or unpublished, that were available by August 1996. RESULTS: None of the interventions has been reliably shown to reduce death or disability after severe head injury. One trial of hyperventilation was identified of 77 participants. The relative risk for death was 0.73 (95% confidence interval (95% CI) 0.36-1.49), and for death or disability it was 1.14 (95% CI 0.82-1.58). One trial of mannitol was identified of 41 participants. The relative risk for death was 1.75 (95% CI 0.48-6.38), no data were available for disability. No randomised trials of CSF drainage were identified. Two randomised trials of barbiturate therapy were identified, including 126 participants. The pooled relative risk for death was 1.12 (95% CI 0.81-1.54). Disability data were available for one trial. The relative risk for death or disability was 0.96 (95% CI 0.62-1.49). Thirteen randomised trials of corticosteroids were identified, comprising 2073 participants. The pooled relative risk for death was 0.95 (0.84 to 1.07) and for death or disability it was 1.01 (95% CI 0.91 to 1.11). On the basis of the currently available randomised evidence, for every intervention studied it is impossible to refute either a moderate increase or a moderate decrease in the risk of death or disability. CONCLUSION: Existing trials have been too small to support or refute the existence of a real benefit from using hyperventilation, mannitol, CSF drainage, barbiturates, or corticosteroids. Further large scale randomised trials of these interventions are required.

Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials.

OBJECTIVE: To determine the effect on mortality of rescuscitation with colloid solutions compared with resuscitation with crystalloids. DESIGN: Systematic review of randomised controlled trials of resuscitation with colloids compared with crystalloids for volume replacement of critically ill patients; analysis stratified according to patient type and quality of allocation concealment. SUBJECTS: 37 randomised controlled trials were eligible, of which 26 unconfounded trials compared colloids with crystalloids (n = 1622). (The 10 trials that compared colloid in hypertonic crystalloid with isotonic crystalloid (n = 1422) and one trial that compared colloid in isotonic crystalloid with hypertonic crystalloid (n = 38) are described in the longer version on our website www.bmj.com). MAIN OUTCOME MEASURES: Mortality from all causes at end of follow up for each trial. RESULTS: Resuscitation with colloids was associated with an increased absolute risk of mortality of 4% (95% confidence interval 0% to 8%), or four extra deaths for every 100 patients resuscitated. The summary effect measure shifted towards increased mortality with colloids when only trials with adequate concealment of allocation were included. There was no evidence for differences in effect among patients with different types of injury that required fluid resuscitation. CONCLUSIONS: This systematic review does not support the continued use of colloids for volume replacement in critically ill patients.

Prophylactic antiepileptic agents after head injury: a systematic review.

OBJECTIVE: To determine the effectiveness and safety of prophylactic antiepileptic agents in the management of acute traumatic head injury. METHODS: Systematic review of randomised controlled trials identified using MEDLINE, EMBASE, CINAHL, Dewent Biotechnology abstracts, and specialised databases of randomised controlled trials, by searching reference lists and contacting investigators. RESULTS: Ten eligible randomised controlled trials were identified, including 2036 patients. The pooled relative risk (RR) for early seizure prevention was 0.34 (95% confidence interval (95%CI) 0.21-0.54); based on this estimate, for every 100 patients treated, 10 would be kept seizure free in the first week. Seizure control in the acute phase was not accompanied by a reduction in mortality (RR=1.15; 95% CI 0.89-1.51), a reduction in death and neurological disability (RR=1.49; 95% CI 1.06-2.08 for carbamazepine and RR=0.96; 95% CI 0.72-1.26 for phenytoin) or a reduction in late seizures (pooled RR=1.28; 95% CI 0.90-1.81). The pooled relative risk for skin rashes was 1.57 (95% CI 0.90-2.75). CONCLUSIONS: Prophylactic antiepileptic drugs are effective in reducing early seizures, but there is no evidence that treatment with such drugs reduces the occurrence of late seizures, or has any effect on death and neurological disability. Insufficient evidence is available to establish the net benefit of prophylactic treatment at any time after injury.

A case control study of breast cancer risk and exposure to injectable progestogen contraceptives. Methods and patterns of use among controls.

OBJECTIVE: To describe the patterns of use of injectable progestogen contraceptives (IPCs) among coloured and black women in the Western Cape. These data are part of an ongoing study in the Western Cape, the main aim of which is to explore the relationship between IPCs and breast cancer. DESIGN: A population-based case-control study of breast cancer risk in relation to the use of IPCs among coloured and black women. SETTING: The Western Cape, including the Cape metropole and surrounding rural areas. STUDY SUBJECTS: All coloured and black women with newly diagnosed breast cancer, resident in the study area and below age 55 years, who present at either of the two tertiary care hospitals in the Western Cape are recruited. Controls are a sample of hospitalised patients representative of the populations from which the patients are drawn. Cases are frequency-matched to controls according to cross-tabulation of age, ethnic group and residential area in a ratio of approximately 1:3. MEASUREMENTS: Questionnaires are administered by trained nurse interviewers, information is elicited on a wide range of variables, including sociodemographic variables, medical history, family history of breast disease, lifetime history of all methods of contraception and use of non-contraceptive female steroids, reproductive variables, cigarette smoking, alcohol consumption and other potentially confounding variables. RESULTS: Between January and December 1994, 122 incident cases and 389 controls were enrolled. Ever-use of IPCs among the controls was 72% (N = 280) and use for 5 years or more was 30% (N = 117). Use of IPCs in the distant past was common, with 61% (N = 232) of all controls having initiated use 10 or more years previously. Current use was also high (19%). Other contraceptive methods were used far less commonly. CONCLUSION: Coloured and black women in South Africa have been using and continue to use IPCs for more commonly and for longer periods than women anywhere else in the world. It is therefore especially important to evaluate the risk of breast cancer and other health effects of IPCs. The rates of use identified in this study ensure that there will be adequate statistical power to evaluate long-term use, use in the distant past and current use of IPCs.

Prevalence of occupational lung disease among Botswana men formerly employed in the South African mining industry.

OBJECTIVE: To determine whether previous health experiences affect the prevalence of occupational lung disease in a semirural Botswanan community where there is a long history of labour recruitment to South African mines. METHOD: A cross sectional prevalence study of 304 former miners examined according to a protocol including a questionnaire, chest radiograph, spirometry, and medical examination. RESULTS: Overall mean age was 56.7 (range 28-93) years, mean duration of service 15.5 (range 2-42) years. 26.6% had a history of tuberculosis. 23.3% had experienced a disabling occupational injury. Overall prevalence of pnemoconiosis (> 1/0 profusion, by the International Labour Organisation classification) was 26.6%-31.0%, and 6.8% had progressive massive fibrosis (PMF). Many were entitled to compensation under South African law. Both radiograph readers detected time response relations between pneumoconiosis and PMF among the 234 underground gold miners. PMF could result from < 5 years of exposure, but was not found < 15 years after first exposure. Both pulmonary tuberculosis (PTB) and pneumoconiosis were found to be associated with airflow limitation. CONCLUSIONS: Former miners in Botswana have a high prevalence of previously unrecognised pneumoconiosis, indicative of high previous exposures to fibrogenic respirable dust. Their pneumoconiosis went unrecognised because they had no access to surveillance after employment. Inadequate radiographic surveillance or failure to act on results when employed or when leaving employment at the mines could have contributed to under recognition. Community based studies of former miners are essential to fully evaluate the effects of mining exposures. Our findings indicate a failure of established measures to prevent or identify pneumoconiosis while these miners were in employment and show that few of the social costs of occupational lung diseases are borne by mining companies through the compensation system.