Stephen Pj Macdonald

Comparison of PIRO, SOFA, and MEDS Scores for Predicting Mortality in Emergency Department Patients With Severe Sepsis and Septic Shock

OBJECTIVES The Predisposition Insult Response and Organ failure (PIRO) scoring system has been developed for use in the emergency department (ED) to risk stratify sepsis cases, but has not been well studied among high-risk patients with severe sepsis and septic shock. The PIRO score was compared with the Sequential Organ Failure Assessment (SOFA) and Mortality in ED Sepsis (MEDS) scores to predict mortality in ED patients with features suggesting severe sepsis or septic shock in the ED. METHODS This was an analysis of sepsis patients enrolled in a prospective observational ED study of patients presenting with evidence of shock, hypoxemia, or other organ failure. PIRO, MEDS, and SOFA scores were calculated from ED data. Analysis compared areas under the receiver operator characteristic (ROC) curves for 30-day mortality. RESULTS Of 240 enrolled patients, final diagnoses were septic shock in 128 (53%), severe sepsis without shock in 70 (29%), and infection with no organ dysfunction in 42 (18%). Forty-eight (20%) patients died within 30 days of presentation. Area under the ROC curve (AUC) for mortality was 0.86 (95% confidence interval [CI] = 0.80 to 0.92) for PIRO, 0.81 (95% CI = 0.74 to 0.88) for MEDS, and 0.78 (95% CI = 0.71 to 0.87) for SOFA scores. Pairwise comparisons of the AUC were as follows: PIRO versus SOFA, p = 0.01; PIRO versus MEDS, p = 0.064; and MEDS versus SOFA; p = 0.37. Mortality increased with increasing PIRO scores: PIRO < 5, 0%; PIRO 5 to 9, 5%; PIRO 10 to 14, 5%; PIRO 15 to 19, 37%; and PIRO ≥ 20, 80% (p < 0.001). The MEDS score also showed increasing mortality with higher scores: MEDS < 5, 0%; MEDS 5 to 7, 12%; MEDS 8 to 11, 15%; MEDS 12 to 14, 48%; and MEDS > 15, 65% (p < 0.001). CONCLUSIONS The PIRO model, taking into account comorbidities and septic source as well as physiologic status, performed better than the SOFA score and similarly to the MEDS score for predicting mortality in ED patients with severe sepsis and septic shock. These findings have implications for identifying and managing high-risk patients and for the design of clinical trials in sepsis.

Sustained elevation of resistin, NGAL and IL-8 are associated with severe sepsis/septic shock in the emergency department.

Objective To identify biomarkers which distinguish severe sepsis/septic shock from uncomplicated sepsis in the Emergency Department (ED). Methods Patients with sepsis underwent serial blood sampling, including arrival in the ED and up to three subsequent time points over the first 24 hours. Messenger RNA (mRNA) levels of 13 genes representing arms of the innate immune response, organ dysfunction or shock were measured in peripheral blood leucocytes using quantitative PCR, and compared with healthy controls. Serum protein concentrations of targets differentially expressed between uncomplicated sepsis and severe sepsis/septic shock were then measured at each time point and compared between the two patient groups. Results Of 27 participants (median age 66 years, (IQR 35, 78)), 10 had uncomplicated sepsis and 17 had sepsis with organ failure (14 septic shock; 3 had other sepsis-related organ failures). At the time of first sample collection in the ED, gene expression of Interleukin (IL)-10 and Neutrophil Gelatinase Associated Lipocalin (NGAL) were significantly higher in severe sepsis than uncomplicated sepsis. Expression did not significantly change over time for any target gene. Serum concentrations of IL-6, IL-8, IL-10, NGAL and Resistin were significantly higher in severe sepsis than uncomplicated sepsis at the time of first sample collection in the ED, but only IL-8, NGAL and Resistin were consistently higher in severe sepsis compared to uncomplicated sepsis at all time points up to 24 h after presentation. Conclusions These mediators, produced by both damaged tissues and circulating leukocytes, may have important roles in the development of severe sepsis. Further work will determine whether they have any value, in addition to clinical risk parameters, for the early identification of patients that will subsequently deteriorate and/or have a higher risk of death.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) predicts renal injury in acute decompensated cardiac failure: a prospective observational study

BackgroundAcute Decompensated Cardiac Failure (ADCF) is frequently associated with deterioration in renal function. Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of kidney injury. We aimed to determine if NGAL measured at admission predicts in-hospital acute kidney injury (AKI) in ADCF.MethodsA prospective observational study measured NGAL and B-natriuretic peptide (BNP) from patients with ADCF presenting to two tertiary hospitals. Patients received standard care and were followed up daily as inpatients. ADCF was defined by PRIDE score ≥ 6 and AKI by RIFLE criteria.ResultsOne hundred and two patients (median age 80, IQR 69-84 years, 52% male) were enrolled. AKI developed in 22 (25%) of 90 for whom outcome data was available. Seven patients died. NGAL was significantly elevated in those who developed AKI versus those who did not (median 130 ng/ml vs 69 ng/ml, p = 0.002). NGAL was also higher in those who died (median 136 ng/ml vs 68 ng/ml, p = 0.005). AKI was significantly associated with risk of death (5/22 (23%) vs 1/68 (1.5%), p = 0.001), but not length of hospital stay. NGAL significantly correlated with admission eGFR but not BNP. For prediction of AKI, NGAL > 89 ng/ml had sensitivity of 68% and specificity of 70% with area under the receiver operator characteristic (ROC) curve of 0.71 (0.58-0.84). After adjustment for baseline renal function, the odds ratio (OR) for AKI was 3.73 (1.26-11.01) if admission NGAL > 89 ng/ml.ConclusionsElevated NGAL at admission is associated with in-hospital AKI and mortality in patients with ADCF. However, it has only moderate diagnostic accuracy in this setting.

Randomized controlled trial of intravenous antivenom versus placebo for latrodectism: The second redback antivenom evaluation (RAVE-II) study

STUDY OBJECTIVE Latrodectism is the most important spider envenomation syndrome worldwide. There remains considerable controversy over antivenom treatment. We aimed to investigate whether antivenom resulted in resolution of pain and systemic effects in patients with latrodectism who received standardized analgesia. METHODS In a multicenter randomized placebo-controlled trial of redback spider antivenom for latrodectism, 224 patients (>7 years) with a redback spider bite and severe pain, with or without systemic effects, were randomized to receive normal saline solution (placebo) or antivenom after receiving standardized analgesia. The primary outcome was a clinically significant reduction in pain 2 hours after trial medication compared with baseline. A second primary outcome for the subgroup with systemic features of envenomation was resolution of systemic features at 2 hours. Secondary outcomes were improved pain at 4 and 24 hours, resolution of systemic features at 4 hours, administration of opioid analgesics or unblinded antivenom after 2 hours, and adverse reactions. RESULTS Two hours after treatment, 26 of 112 patients (23%) from the placebo arm had a clinically significant improvement in pain versus 38 of 112 (34%) from the antivenom arm (difference in favor of antivenom 10.7%; 95% confidence interval -1.1% to 22.6%; P=.10). Systemic effects resolved after 2 hours in 9 of 41 patients (22%) in the placebo arm and 9 of 35 (26%) in the antivenom arm (difference 3.8%; 95% confidence interval -15% to 23%; P=.79). There was no significant difference in any secondary outcome between antivenom and placebo. Acute systemic hypersensitivity reactions occurred in 4 of 112 patients (3.6%) receiving antivenom. CONCLUSION The addition of antivenom to standardized analgesia in patients with latrodectism did not significantly improve pain or systemic effects.

Comparison of two clinical scoring systems for emergency department risk stratification of suspected acute coronary syndrome

Objective: To compare two methods of risk stratification for suspected acute coronary syndrome (ACS) in the ED.

Rapid risk stratification in suspected acute coronary syndrome using serial multiple cardiac biomarkers: A pilot study

Objective:  To determine the feasibility of using a biomarker panel of myoglobin, creatinine kinase MB (CK‐MB) and cardiac troponin I (cTnI) to identify patients with suspected acute coronary syndrome (ACS) who are suitable for discharge within 2 h.

Near-infrared spectroscopy in the assessment of suspected sepsis in the emergency department

Background and aims The conventional approach to sepsis resuscitation involves early interventions targeting global oxygenation and macro-haemodynamic variables such as central venous and systemic arterial pressures. There is increasing recognition of the importance of microcirculatory changes in shock states, including sepsis, and the relationship of these to outcome. Near-infrared spectroscopy (NIRS) is a recently developed non-invasive technology that measures tissue oxygen saturations (StO2), which may be an indirect measure of the adequacy of the microcirculation. StO2 measurements, therefore, have the potential to identify patients who are at risk of progressing to organ dysfunction and could be used to guide resuscitation. This article reviews the current state of knowledge of NIRS in the setting of sepsis, examining its application, validity and prognostic value. Methods A search of the relevant literature was performed using Medline, Embase and Cochrane databases, and a qualitative analysis was undertaken. Results A limited number of observational studies, mostly conducted among patients with severe sepsis, have shown that NIRS may correlate with severity of illness but demonstrate a variable relationship between StO2 and outcome. Conclusions Outstanding questions still remain as to whether NIRS can help to risk-stratify patients with suspected sepsis in the emergency department and the utility of StO2 as a resuscitation target.

Do risks outweigh benefits in thrombolysis for stroke

Simon Brown and Stephen Macdonald argue that patients with stroke should not be given thrombolysis outside clinical trials, but Graeme Hankey says the benefits are clear in carefully selected patients

Modified TIMI risk score cannot be used to identify low-risk chest pain in the emergency department: a multicentre validation study

Aim The Thrombolysis in Myocardial Infarction (TIMI) risk score (range 0–7), used for emergency department (ED) risk stratification of patients with suspected acute coronary syndrome (ACS), underestimates risk associated with ECG changes or cardiac troponin elevation. A modified TIMI score (mTIMI, range 0–10), which gives increased weighting to these variables, has been proposed. We aimed to evaluate the performance of the mTIMI score in ED patients with suspected ACS. Methods A multicentre prospective observational study enrolled patients undergoing assessment for possible ACS. TIMI and mTIMI scores were calculated. The study outcome was a composite of all-cause death, myocardial infarction or coronary revascularisation within 30 days. Results Of the 1666 patients, 219 (13%) reached the study outcome. Area under the receiver operating characteristic curve for the composite outcome was 0.80 (0.76 to 0.83) for the mTIMI score compared with 0.71 (0.67 to 0.74) for the standard TIMI score, p<0.001, but there was no significant difference for death or revascularisation outcomes. Sensitivity and specificity for the composite outcome were 0.96 (0.92 to 0.98) and 0.23 (0.20 to 0.26), respectively, at score 0 for TIMI and mTIMI. At score <2, sensitivity and specificity were 0.82 (0.77 to 0.87) and 0.53 (0.51 to 0.56) for mTIMI, and 0.74 (0.68 to 0.79) and 0.54 (0.51 to 0.56) for standard TIMI, respectively. Conclusions mTIMI score performs better than standard TIMI score for ED risk stratification of chest pain, but neither is sufficiently sensitive at scores >0 to allow safe and early discharge without further investigation or follow-up. Observed differences in performance may be due to incorporation bias.

Spontaneous pneumothorax; a multicentre retrospective analysis of emergency treatment, complications and outcomes

Spontaneous pneumothorax can be managed initially by observation, aspiration or chest drain insertion.