A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators.

PURPOSE: To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. METHODS: Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. RESULTS: From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2% [495/2134] versus control: 22.4% [582/2601]; pooled OR 1.01 [95% CI 0.88-1.16], P = 0.9, with heterogeneity [I(2) = 57%; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95% CI 0.86-1.15), P = 0.93] with no heterogeneity (I(2) = 0.0%; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95% CI 1.10-1.41]; P < 0.001) and ICU admission [OR 2.19 (95% CI 1.82-2.65); P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I(2) = 71%; P < 0.001) but did not change overall results [pooled OR 0.94 (95% CI 0.82 to 1.07); P = 0.33]. CONCLUSION: EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

A randomised controlled trial of intramuscular vs. intravenous antivenom for latrodectism--the RAVE study.

BACKGROUND: Widow spider-bite causes latrodectism and is associated with significant morbidity worldwide. Antivenom is given by both the intravenous (IV) and intramuscular (IM) routes and it is unclear which is more effective. AIM: To compare the effectiveness of IV vs. IM redback spider antivenom. DESIGN: Randomized controlled trial. METHODS: Patients with latrodectism were given either IV or IM antivenom according to a randomized double-dummy, double-blind protocol. The first antivenom treatment was followed by another identical treatment after two hours if required. The primary outcome was a clinically significant reduction in pain two hours after the last treatment. A fully Bayesian analysis was used to estimate the probability of the desired treatment effect, predetermined as an absolute difference of 20%. RESULTS: We randomly allocated 126 patients to receive antivenom IV (64) and IM (62). After antivenom treatment pain improved in 40/64(62%) in the IV group vs. 33/62(53%) in the IM group (+9%; 95% Credible Interval [CrI]: -8% to +26%). The probability of a difference greater than zero (IV superior) was 85% but the probability of a difference >20% was only 10%. In 55 patients with systemic effects, these improved in 58% after IV antivenom vs. 65% after IM antivenom (-8%; 95% CrI: -32% to +17%). Twenty-four hours after antivenom pain had improved in 84% in the IV group vs. 71% in the IM group (+13%; 95% CrI: -2% to +27%). A meta-analysis including data from a previous trial found no difference in the primary outcome between IV and IM administration. DISCUSSION: The difference between IV and IM routes of administration of widow spider antivenom is, at best, small and does not justify routinely choosing one route over the other. Furthermore, antivenom may provide no benefit over placebo.

A comparison of tape-tying versus a tube-holding device for securing endotracheal tubes in adults.

During the transfer of intubated patients, endotracheal tube security is paramount. This study aims to compare two methods of securing an endotracheal tube in adults: tying with a cloth tape versus the Thomas Endotracheal Tube Holder (Laerdal). A manikin-based study was performed using paramedics and critical care doctors (consultants and senior trainees) as participants. Each participant was asked to secure an endotracheal tube that had been placed within the trachea of a manikin a total of six times, the first three times using tied cloth tape and the last three times using a Thomas Endotracheal Tube Holder. Following each 'fixation' and after the participant had left the room, the security of the tube was tested by applying a fixed force laterally and to the right by dropping a 1.25 kg weight a distance of 50 cm. The amount of movement of the tube with respect to the teeth was measured and recorded in millimetres. Two-hundred-and-seventy tube fixations (135 tied vs. 135 tube holder) were performed by 45 participants. The degree of tube movement was significantly higher when the tube was secured with a tie compared with when the tube holder was used (median movement 22 mm vs. 4 mm, P < 0.0001). We have demonstrated that the tube holder device minimised tube movement in a manikin model when compared with conventional tape tying. The use of this device when transporting intubated patients may reduce the risk of tube displacement though further clinical studies are warranted.

Adenosine versus intravenous calcium channel antagonists for the treatment of supraventricular tachycardia in adults.

BACKGROUND: Patients with paroxysmal supraventricular tachycardia frequently present to the Emergency Department. Where vagal manoeuvres fail, the two most commonly used drugs are adenosine and calcium channel antagonists. Both are known to be effective but both have a significant side-effect profile. OBJECTIVES: To examine the relative effects of adenosine and calcium channel antagonists and, if possible, to determine which is most appropriate for the management of supraventricular tachycardia. SEARCH STRATEGY: Studies were identified from The Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3 2006, MEDLINE (1966 to June 2006), Pre-MEDLINE and EMBASE (1980 to June 2006). Bibliographies of identified studies were also examined. No language restrictions were applied. INCLUSION CRITERIA: randomised trials comparing adenosine and a calcium channel antagonist in patients of any age with supraventricular tachycardia, where one of the defined outcomes was reported. Outcomes of interest were: reversion rate, mortality, time to reversion, rate of relapse, minor adverse events, major adverse events, length of hospital stay and patient satisfaction. Major adverse events were defined as cardiac arrest, prolonged hypotension, symptomatic bradycardia requiring treatment and acute cardiac failure. Minor adverse events were any other reported event. DATA COLLECTION AND ANALYSIS: Two reviewers independently checked the results of searches to identify relevant studies. Dichotomous outcomes were reported as Peto Odds ratios and continuous outcomes as weighted mean differences. MAIN RESULTS: Eight trials were identified. In the pooled analysis there was no significant difference in reversion rate or relapse rate between the two drugs. Time to reversion was slower for verapamil than adenosine in all studies that reported this outcome, but the data were not suitable for combining. Minor adverse events such as nausea, chest tightness, shortness of breath and headache were reported much more frequently in patients treated with adenosine with 10.8 % of patients reporting at least one of these events, compared with 0.6% of those treated with verapamil (OR 0.15, 95% CI 0.09 to 0.26, P<0.001). There was no significant difference in the rate of major adverse events between the two groups, although hypotension was reported exclusively in the verapamil treatment group (3/166 patients treated with verapamil, 0/171 treated with adenosine). AUTHORS' CONCLUSIONS: Adenosine and verapamil are both effective treatments for supraventricular tachycardia in the majority of patients. However, given the high incidence of minor but unpleasant side effects in patients treated with adenosine and the potential for hypotension with verapamil, patients should be fully informed of these risks prior to treatment.

Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic.

BACKGROUND: Renal colic is a common cause of acute severe pain. Both opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for treatment, but the relative efficacy of these drugs is uncertain. OBJECTIVES: To examine the benefits and disadvantages of NSAIDs and opioids for the management of pain in acute renal colic. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register (May 2003), the Cochrane Central Register of Randomised Controlled Trials (CENTRAL - The Cochrane Library issue 2, 2003), MEDLINE (1966 - 31 January 2003), EMBASE (1980 - 31 January 2003) and handsearched reference lists of retrieved articles. Most recent search date: January 2005 SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any opioid with any NSAID, regardless of dose or route of administration were included. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. Subgroup analysis by study quality, drug type and drug route have been performed where possible to explore reasons for heterogeneity. MAIN RESULTS: Twenty trials from nine countries with a total of 1613 participants were identified. Both NSAIDs and opioids lead to clinically significant falls in patient-reported pain scores. Due to unexplained heterogeneity these results could not be pooled although 10/13 studies reported lower pain scores in patients receiving NSAIDs. Patients treated with NSAIDs were significantly less likely to require rescue medication (RR 0.75, 95% CI 0.61 to 0.93, P = 0.007), though most of these trials used pethidine. The majority of trials showed a higher incidence of adverse events in patients treated with opioids, but there was significant heterogeneity between studies so the results could not be pooled. There was significantly less vomiting in patients treated with NSAIDs (RR 0.35, 95% CI 0.23 to 0.53, P < 0.00001). In particular, patients receiving pethidine had a much higher rate of vomiting compared with patients receiving NSAIDs. Gastrointestinal bleeding and renal impairment were not reported. AUTHORS' CONCLUSIONS: Both NSAIDs and opioids can provide effective analgesia in acute renal colic. Opioids are associated with a higher incidence of adverse events, particularly vomiting. Given the high rate of vomiting associated with the use of opioids, particularly pethidine, and the greater likelihood of requiring further analgesia, we recommend that if an opioid is to be used it should not be pethidine.

Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic.

BACKGROUND: Renal colic is a common cause of acute severe pain. Both opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for treatment, but the relative efficacy of these drugs is uncertain. OBJECTIVES: To examine the benefits and disadvantages of NSAIDs and opioids for the management of pain in acute renal colic. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register (May 2003), the Cochrane Central Register of Randomised Controlled Trials (CENTRAL - The Cochrane Library issue 2, 2003), MEDLINE (1966 - 31 January 2003), EMBASE (1980 - 31 January 2003) and handsearched reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any opioid with any NSAID, regardless of dose or route of administration were included. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. Subgroup analysis by study quality, drug type and drug route have been performed where possible to explore reasons for heterogeneity. MAIN RESULTS: Twenty trials from nine countries with a total of 1613 participants were identified. Both NSAIDs and opioids lead to clinically significant falls in patient-reported pain scores. Due to unexplained heterogeneity these results could not be pooled although 10/13 studies reported lower pain scores in patients receiving NSAIDs. Patients treated with NSAIDs were significantly less likely to require rescue medication (RR 0.75, 95% CI 0.61 to 0.93, P = 0.007), though most of these trials used pethidine. The majority of trials showed a higher incidence of adverse events in patients treated with opioids, but there was significant heterogeneity between studies so the results could not be pooled. There was significantly less vomiting in patients treated with NSAIDs (RR 0.35, 95% CI 0.23 to 0.53, P < 0.00001). In particular, patients receiving pethidine had a much higher rate of vomiting compared with patients receiving NSAIDs. Gastrointestinal bleeding and renal impairment were not reported. REVIEWER'S CONCLUSIONS: Both NSAIDs and opioids can provide effective analgesia in acute renal colic. Opioids are associated with a higher incidence of adverse events, particularly vomiting. Given the high rate of vomiting associated with the use of opioids, particularly pethidine, and the greater likelihood of requiring further analgesia, we recommend that if an opioid is to be used it should not be pethidine.

Perils and pitfalls of lumbar puncture in the emergency department.

Lumbar Puncture is a procedure commonly performed in the emergency department. It provides important diagnostic information but has a significant number of limitations and complications. This article reviews the role of lumbar puncture in the emergency department based on an extensive review of the current literature, focusing on the recognized contraindications and complications of the procedure and how they can be minimized. The interpretation of diagnostic tests performed on cerebrospinal fluid is also examined, highlighting those tests most commonly ordered from the emergency department.

Does local anaesthetic affect the success rate of intravenous cannulation?

We aimed to assess whether subcutaneous lignocaine affects the success rate of intravenous cannulation using a randomized clinical trial. Pre-prepared cannulation packs, 50% containing local anaesthetic, were used to cannulate consecutive consenting patients presenting to the Emergency Department who required cannulation as part of their routine treatment. Doctors with less than four years postgraduate experience randomly selected a pack to perform cannulation and completed a data collection form after each cannulation. Eighty-seven patients received lignocaine with 73 (83.9%) successfully cannulated on the first attempt, 79 patients were cannulated without lignocaine with 64 (81%) successfully cannulated on the first attempt. Subcutaneous lignocaine did not significantly affect the success rate of intravenous cannulation on the first attempt (P = 0.5). Subcutaneous lignocaine has been shown to significantly reduce the pain of intravenous cannulation. This study supports the use of local anaesthesia for all routine venous cannulation.