Anna Holdgate

Goal-directed resuscitation for patients with early septic shock.

BACKGROUND Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain. METHODS In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization. RESULTS Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay. CONCLUSIONS In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. (Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation; ARISE ClinicalTrials.gov number, NCT00975793.).

Systematic review of the relative efficacy of non-steroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic

Abstract Objective To examine the relative benefits and disadvantages of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids for the management of acute renal colic. Data sources Cochrane Renal Groups specialised register, Cochrane central register of controlled trials, Medline, Embase, and reference lists of retrieved articles. Review methods Randomised controlled trials comparing any opioid with any NSAID in acute renal colic if they reported any of the following outcomes: patient rated pain, time to pain relief, need for rescue analgesia, rate of recurrence of pain, and adverse events. Results 20 trials totalling 1613 participants were identified. Both NSAIDs and opioids led to clinically important reductions in patient reported pain scores. Pooled analysis of six trials showed a greater reduction in pain scores for patients treated with NSAIDs than with opioids. Patients treated with NSAIDs were significantly less likely to require rescue analgesia (relative risk 0.75, 95% confidence interval 0.61 to 0.93). Most trials showed a higher incidence of adverse events in patients treated with opioids. Compared with patients treated with opioids, those treated with NSAIDs had significantly less vomiting (0.35, 0.23 to 0.53). Pethidine was associated with a higher rate of vomiting. Conclusions Patients receiving NSAIDs achieve greater reductions in pain scores and are less likely to require further analgesia in the short term than those receiving opioids. Opioids, particularly pethidine, are associated with a higher rate of vomiting.

Anaphylaxis: clinical patterns, mediator release, and severity.

BACKGROUND Prospective human studies of anaphylaxis and its mechanisms have been limited, with few severe cases or examining only 1 or 2 mediators. OBJECTIVES We wanted to define the clinical patterns of anaphylaxis and relationships between mediators and severity. METHODS Data were collected during treatment and before discharge. Serial blood samples were taken for assays of mast cell tryptase, histamine, anaphylatoxins (C3a, C4a, C5a), cytokines (IL-2, IL-6, IL-10), soluble tumor necrosis factor receptor I, and platelet activating factor acetyl hydrolase. Principal component analysis defined mediator patterns, and logistic regression identified risk factors and mediator patterns associated with reaction severity and delayed reactions. RESULTS Of 412 reactions in 402 people, 315 met the definition for anaphylaxis by the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network. Of 97 severe reactions 45 (46%) were hypotensive, 23 (24%) were hypoxemic, and 29 (30%) were mixed. One patient died. Severe reactions were associated with older age, pre-existing lung disease, and drug causation. Delayed deteriorations treated with epinephrine occurred in 29 of 315 anaphylaxis cases (9.2%) and were more common after hypotensive reactions and with pre-existing lung disease. Twenty-two of the 29 delayed deteriorations (76%) occurred within 4 hours of initial epinephrine treatment. Of the remaining 7 cases, 2 were severe and occurred after initially severe reactions, within 10 hours. All mediators were associated with severity, and 1 group (mast cell tryptase, histamine, IL-6, IL-10, and tumor necrosis factor receptor I) was also associated with delayed deteriorations. Low platelet activating factor acetyl hydrolase activity was associated with severe reactions. CONCLUSION The results suggest that multiple inflammatory pathways drive reaction severity and support recommendations for safe observation periods after initial treatment.

Variability in agreement between physicians and nurses when measuring the Glasgow Coma Scale in the emergency department limits its clinical usefulness

Objective:  To assess the interrater reliability of the Glasgow Coma Scale (GCS) between nurses and senior doctors in the ED.

Elevated serum cytokines during human anaphylaxis: Identification of potential mediators of acute allergic reactions

BACKGROUND Anaphylaxis is generally unanticipated and requires emergency management. Therefore, the biological mediators in human beings have been difficult to define. OBJECTIVE Our aim was to identify cytokines and chemokines whose concentrations increase during anaphylaxis in human beings and to determine how each correlates with severity. METHODS We measured the concentrations of potential mediators, including cytokines, chemokines, mast cell tryptase (MCT), and histamine, over 3 time points in 76 patients presenting to emergency departments with anaphylaxis and correlated these with a global severity scale, hypotension, and hypoxia. RESULTS IL-2, IL-6, IL-10, TNF receptor I, MCT, and histamine were significantly elevated in patients with severe reactions (n = 36) compared with moderate reactions (n = 40) and healthy controls. Histamine levels peaked at emergency department arrival, whereas other mediators peaked later. IL-4, IL-5, IL-13, IFN-gamma, and TNF-alpha were marginally elevated in severe reactions compared with healthy controls but did not correlate with reaction severity. Severe reactions tended to be either hypotensive (n = 19) or hypoxemic (n = 12). Levels of IL-6, IL-10, TNF receptor I, MCT, and histamine correlated with hypotension. No mediator correlated with hypoxemia or other respiratory features. CONCLUSION This study confirms that the concentrations of a number of cytokines are elevated in blood during anaphylaxis in human beings and that some correlate with the presence of hypotension. Others were only marginally elevated within a concentration range that available assays do not reliably detect. During respiratory reactions, mediators may be largely confined to the airways so that blood concentrations do not reflect activity.

The Implementation of Intranasal Fentanyl for Children in a Mixed Adult and Pediatric Emergency Department Reduces Time to Analgesic Administration

OBJECTIVES The objective was to determine whether the introduction of intranasal (IN) fentanyl for children with acute pain would reduce the time to analgesic administration in a mixed adult and pediatric emergency department (ED). METHODS A protocol for IN fentanyl (1.5 microg/ kg) for children age 1-15 years presenting with acute pain was introduced to the department. All children who received intravenous (IV) morphine in the 7 months prior to the introduction of the protocol and either IV morphine or IN fentanyl in the 7 months after the introduction of the protocol were identified from drug registers. Time to analgesic administration, time to see a doctor, and the ages of patients were compared between the periods before and after the introduction of IN fentanyl. RESULTS Following implementation, 81 patients received IN fentanyl and 37 received IV morphine, compared to 63 patients receiving morphine in the previous 7 months. The median time to analgesic administration for IN fentanyl was significantly shorter than for morphine (32 minutes vs. 63 minutes, p = 0.001). Children receiving fentanyl were significantly younger than those receiving morphine (median = 8.5 years vs. 12 years, p < 0.001). CONCLUSIONS This study demonstrates that children treated with IN fentanyl received analgesic medication faster than those treated with IV morphine in a mixed ED. Younger children were more likely to receive opioid analgesia following the introduction of fentanyl.

Patterns of analgesia for fractured neck of femur in Australian emergency departments

Objectives:  Fractured neck of femur is a common ED problem and poor pain management in this patient group can contribute significantly to their morbidity. The present study aims to describe current practices for managing pain in patients with fractured neck of femur in Australian ED and to identify real or potential barriers to providing analgesia.

Validation of emergency physician ultrasound in diagnosing hydronephrosis in ureteric colic

Objective:  Patients presenting to the ED with obstructive nephropathies benefit from early detection of hydronephrosis. Out of hours radiological imaging is expensive and disruptive to arrange. Emergency physician ultrasound (EPU) could allow rapid diagnosis and disposition. If accurate it might avert the need for formal radiological imaging, exclude an obstruction and improve patient flow through the ED.

Accuracy of ECG electrode placement by emergency department clinicians

Objectives:  Misplaced ECG electrodes can cause changes in ECG recordings, which could have an impact on clinical decisions. We aimed to determine the inter‐rater reliability of ECG electrode placement by senior clinical staff in the ED.

Risk factors for sedation-related events during procedural sedation in the emergency department

Objective: To determine the nature, incidence and risk factors for sedation‐related events during ED procedural sedation, with particular focus on the drugs administered.