Majid Afshar

Narrative review: tetanus--a health threat after natural disasters in developing countries

Tetanus is an expected complication when disasters strike in developing countries, where tetanus immunization coverage is often low or nonexistent. Collapsing structures and swirling debris inflict numerous crush injuries, fractures, and serious wounds. Clostridium tetani infects wounds contaminated with dirt, feces, or saliva and releases neurotoxins that may cause fatal disease. Clusters of infections have recently occurred after tsunamis and earthquakes in Indonesia, Kashmir, and Haiti. The emergency response to clusters of tetanus infections in developing countries after a natural disaster requires a multidisciplinary approach in the absence of an intensive care unit, readily available resources, and a functioning cold-chain system. It is essential that injured people receive immediate surgical and medical care of contaminated, open wounds with immunization and immunoglobulin therapy. Successful treatment of tetanus depends on prompt diagnosis of clinical tetanus, treatment to ensure neutralization of circulating toxin and elimination of C. tetani infection, control of spasms and convulsions, maintenance of the airway, and management of respiratory failure and autonomic dysfunction.

Acute immunomodulatory effects of binge alcohol ingestion

BACKGROUND Blood alcohol is present in a third of trauma patients and has been associated with organ dysfunction. In both human studies and in animal models, it is clear that alcohol intoxication exerts immunomodulatory effects several hours to days after exposure, when blood alcohol is no longer detectable. The early immunomodulatory effects of alcohol while blood alcohol is still elevated are not well understood. METHODS Human volunteers achieved binge alcohol intoxication after high-dose alcohol consumption. Blood was collected for analysis prior to alcohol ingestion, and 20 min, 2 h, and 5 h after alcohol ingestion. Flow cytometry was performed on isolated peripheral blood mononuclear cells, and cytokine generation in whole blood was measured by enzyme-linked immunosorbent assay (ELISA) after 24-h stimulation with lipopolysaccharide (LPS) and phytohemagglutinin-M (PHA) stimulation. RESULTS An early pro-inflammatory state was evident at 20 min when blood alcohol levels were ∼130 mg/dL, which was characterized by an increase in total circulating leukocytes, monocytes, and natural killer cells. During this time, a transient increase in LPS-induced tumor necrosis factor (TNF)-α levels and enhanced LPS sensitivity occurred. At 2 and 5 h post-alcohol binge, an anti-inflammatory state was shown with reduced numbers of circulating monocytes and natural killer cells, attenuated LPS-induced interleukin (IL)-1β levels, and a trend toward increased interleukin (IL)-10 levels. CONCLUSIONS A single episode of binge alcohol intoxication exerted effects on the immune system that caused an early and transient pro-inflammatory state followed by an anti-inflammatory state.

Blood alcohol content, injury severity, and adult respiratory distress syndrome

BACKGROUND Elevated blood alcohol content (BAC) is a risk factor for injury. Associations of BAC with adult respiratory distress syndrome (ARDS) have not been conclusively established. We evaluated the association of a BAC greater than 0 mg/dL with the intermediate outcomes, Injury Severity Score (ISS) and Glasgow Coma Scale (GCS) score, and their association with ARDS development. METHODS This is an observational retrospective cohort study of 26,305 primary trauma admissions to a statewide referral trauma center from July 11, 2003, to October 31, 2011. Logistic regression was performed to assess the relationship between admission BAC, ISS, GCS score, and ARDS development within 5 days of admission. RESULTS The case rate for ARDS was 5.5% (1,447). BAC greater than 0 mg/dL was associated with ARDS development in adjusted analysis (odds ratio, 1.50; 95% confidence interval [CI], 1.33–1.71; p < 0.001). High ISS (≥16) had a stronger association with ARDS development (odds ratio, 17.99; 95% CI, 15.51–20.86), as did low GCS score (⩽8) (odds ratio, 8.77; 95% CI, 7.64–10.07; p < 0.001). Patients with low GCS score and high ISS had the most frequent ARDS (33.6%) and the highest case-fatality rate without ARDS (24.7%). CONCLUSION Elevated BAC is associated with ARDS development. In the analysis of alcohol exposure, ISS and GCS score occur after alcohol ingestion, making them intermediate outcomes. ISS and GCS score were strong predictors of ARDS and may be useful to identify at-risk patients. Elevated BAC may increase the frequency of the ARDS through influence on injury severity or independent molecular mechanisms, which can be discriminated only in experimental models. LEVEL OF EVIDENCE Epidemiologic study, level III.

Alveolar macrophage inflammatory mediator expression is elevated in the setting of alcohol use disorders

Alcohol use disorders (AUDs) are associated with increased susceptibility to pulmonary diseases, including bacterial pneumonia and acute respiratory distress syndrome (ARDS). Alveolar macrophages (AMs) play a vital role in the clearance of pathogens and regulation of inflammation, but these functions may be impaired in the setting of alcohol exposure. We examined the effect of AUDs on profiles of cytokines, chemokines, and growth factors in human AMs isolated from bronchoalveolar lavage (BAL) samples from 19 AUD subjects and 20 age-, sex-, and smoking-matched control subjects. By multiplex bead array, the lysates of AMs from subjects with AUDs had significant elevation in the cytokine tumor necrosis factor α (TNF-α), as well as chemokine (C-X-C motif) ligand 8 (CXCL8), CXCL10, and chemokine (C-C motif) ligand 5 (CCL5) (p < 0.05). Additionally, a 1.8-fold increase in IL-1β, 2.0-fold increase in IL-6, 2.3-fold increase in interferon gamma (IFN-γ), 1.4-fold increase in CCL3, and a 2.3-fold increase in CCL4 was observed in the AUD group as compared to the control group. We also observed compensatory increases in the anti-inflammatory cytokine IL-1RA (p < 0.05). AUD subjects had 5-fold higher levels of CXCL11 mRNA expression (p < 0.05) and a 2.4-fold increase in IL-6 mRNA expression by RT-PCR as well. In these investigations, alcohol use disorders were associated with functional changes in human AMs, suggesting that chronic alcohol exposure portends a chronically pro-inflammatory profile in these cells.

Alcohol exposure, injury, and death in trauma patients.

BACKGROUND The association of alcohol use with in-hospital trauma deaths remains unclear. This study identifies the association of blood alcohol content (BAC) with in-hospital death accounting for injury severity and mechanism. METHODS This study involves a historical cohort of 46,222 admissions to a statewide trauma center between January 1, 2002, and October 31, 2011. Blood alcohol was evaluated as an ordinal variable: 1 mg/dL to 100 mg/dL as moderate blood alcohol, 101 mg/dL to 230 mg/dL as high blood alcohol, and greater than 230 mg/dL as very high blood alcohol. RESULTS Blood alcohol was recorded in 44,502 patients (96.3%). Moderate blood alcohol was associated with an increased odds for both penetrating mechanism (odds ratio [OR], 2.22; 95% confidence interval [CI], 2.04–2.42) and severe injury (OR, 1.25; 95% CI, 1.16–1.35). Very high blood alcohol had a decreased odds for penetrating mechanism (OR, 0.75; 95% CI, 0.67–0.85) compared with the undetectable blood alcohol group. An inverse U-shaped association was shown for severe injury and penetrating mechanism by alcohol group (p < 0.001). Moderate blood alcohol had an increased odds for in-hospital death (OR, 1.50; 95% CI, 1.25–1.79), and the odds decreased for very high blood alcohol (OR, 0.69; 95% CI, 0.54–0.87). An inverse U-shaped association was also shown for in-hospital death by alcohol group (p < 0.001). Model discrimination for in-hospital death had an area under the receiver operating characteristic curve of 0.64 (95% CI, 0.63–0.65). CONCLUSION Injury severity and mechanism are strong intermediate outcomes between alcohol and death. Severe injury itself carried the greatest odds for death, and with the moderate BAC group at greatest odds for severe injury and the very high BAC group at the lowest odds for severe injury. The result was a similar inverse-U shaped curve for odds for in-hospital death. Clear associations between blood alcohol and in-hospital death cannot be analyzed without consideration for the different injuries by blood alcohol groups. LEVEL OF EVIDENCE Epidemiologic study, level III.

Pulmonary Hypertension in Elderly Patients with Diastolic Dysfunction and Preserved Ejection Fraction

Purpose: Patients with diastolic dysfunction may have a disproportionate degree of elevation in pulmonary pressure, particularly in the elderly. Higher pulmonary vascular resistance in the elderly patients with heart failure but preserved ejection fraction suggests that beyond the post-capillary contribution of pulmonary venous congestion, a pre-capillary component of pulmonary arterial hypertension occurs. We aim to identify if pulmonary vascular resistance in elderly patients with diastolic dysfunction is disproportionately higher than patients with systolic dysfunction independent of filling pressures. Methods: 389 patients identified retrospectively between 2003- 2010; elderly with preserved ejection fraction, elderly with depressed ejection fraction, and primary arterial hypertension who underwent right-heart catheterization at Rush University. Results: No significant difference in pulmonary vascular resistance between systolic and diastolic dysfunction. The mean difference in pulmonary vascular resistance was not statistically significant at 0.40 mmHg·min/l (95% CI -3.03 to 3.83) with similar left ventricular filling pressures with mean difference of 3.38 mmHg (95% CI, -1.27 to 8.02). When adjusted for filling pressures, there remained no difference in pulmonary vascular resistance for systolic and diastolic dysfunction. The mean pulmonary vascular resistance is more elevated in systolic heart failure compared to diastolic heart failure with means 3.13 mmHg·min/l and 3.52 mmHg·min/l, respectively. Conclusion: There was no other association identified for secondary pulmonary hypertension other than diastolic dysfunction and chronic venous pulmonary hypertension. Our results argue against any significant arterial remodeling that would lead to disproportionate pre-capillary hypertension, and implies that treatment should focus on lowering filling pressure rather than treating the pulmonary vascular tree.

Injured patients with very high blood alcohol concentrations.

OBJECTIVE Most data regarding high blood alcohol concentrations (BAC) ≥400 mg/dL have been from alcohol poisoning deaths. Few studies have described this group and reported their alcohol consumption patterns or outcomes compared to other trauma patients. We hypothesised trauma patients with very high BACs arrived to the trauma centre with less severe injuries than their sober counterparts. METHOD Historical cohort of 46,222 patients admitted to a major trauma centre between January 1, 2002 and October 31, 2011. BAC was categorised into ordinal groups by 100 mg/dL intervals. Alcohol questionnaire data on frequency and quantity was captured in the BAC ≥400 mg/dL group. The primary analysis was for BAC ≥400 mg/dL. RESULTS BAC was recorded in 44,502 (96.3%) patients. Those with a BAC ≥400 mg/dL accounted for 1.1% (147) of BAC positive cases. These patients had the lowest proportion of severe trauma and in-hospital death in comparison with the other alcohol groups (p<0.001). In adjusted analysis, the risk for severe injury increased with the BAC groups between 1 and 199 mg/dL and was not different or decreased for groups above 200 mg/dL in reference to the BAC negative group (test for trend p=0.001). BAC ≥400 group encountered more injuries caused by blunt trauma in comparison with the other alcohol groups (p<0.001), and the group comprised mainly of falls. Admission Glasgow Coma Scale was a poor predictor for traumatic brain injury in the high BAC group. Readmission occurred in 22.4% (33) of patients the BAC ≥400 group. The majority of these patients reported drinking alcohol 4 or more days per week (81, 67.5%) and five or more drinks per day (79, 65.8%), evident of risky alcohol use. CONCLUSIONS Most traumas admitted with BAC ≥400 mg/dL survived and their injuries were less severe than their less intoxicated and sober counterparts. They also had evidence for risky alcohol use and nearly one-quarter returned to the trauma centre with another injury over the study period. Recognition of this highest BAC group presents an opportunity to provide focused care for their risky alcohol use.

Update in Critical Care for the Nephrologist: Transfusion in Nonhemorrhaging Critically Ill Patients

A growing number of guidelines and recommendations advocate a restrictive transfusion strategy. Strong evidence exists that a hemoglobin threshold of less than 7 g/dL conserves resources and may improve outcomes in critically ill patients and that platelet counts greater than 10,000/μL are well tolerated. Patients with coronary artery disease can be safely managed with a restrictive transfusion strategy, utilizing a hemoglobin threshold of less than 7 or 8 g/dL; a threshold of less than 8 g/dL can be applied to patients with acute coronary syndromes. In the absence of coagulopathy with bleeding or high risk for bleeding, plasma transfusion should be withheld. Complications from transfusion are significant and previously under-recognized immunologic complications pose a more serious threat than infections. Erythropoietin and iron administration do not reduce transfusion needs in the critically ill. Interventions to reduce blood loss and educate clinicians are successful in reducing transfusion requirements.

Nonpharmacologic approach to minimizing shivering during surface cooling: A proof of principle study☆

PURPOSE This study had 2 objectives: (1) to quantify the metabolic response to physical cooling in febrile patients with systemic inflammatory response syndrome (SIRS) and (2) to provide proof for the hypothesis that the efficiency of external cooling and the subsequent shivering response are influenced by site and temperature of surface cooling pads. METHODS To quantify shivering thermogenesis during surface cooling for fever, we monitored oxygen consumption (VO(2)) in 6 febrile patients with SIRS during conventional cooling with cooling blankets and ice packs. To begin to determine how location and temperature of surface cooling influence shivering, we compared 5 cooling protocols for inducing mild hypothermia in 6 healthy volunteers. RESULTS In the patients with SIRS, core temperature decreased 0.67 °C per hour, all patients shivered, VO(2) increased 57.6%, and blood pressure increased 15% during cooling. In healthy subjects, cooling with the 10 °C vest was most comfortable and removed heat most efficiently without shivering or VO(2) increase. Cooling with combined vest and thigh pads stimulated the most shivering and highest VO(2) and increased core temperature. Reducing vest temperature from 10 °C to 5 °C failed to increase heat removal secondary to cutaneous vasoconstriction. Capsaicin, an agonist for the transient receptor potential cation channel subfamily V member 1 (TRPV1) warm-sensing channels, partially reversed this effect in 5 subjects. CONCLUSIONS Our results identify the hazards of surface cooling in febrile critically ill patients and support the concept that optimization of cooling pad temperature and position may improve cooling efficiency and reduce shivering.

Azithromycin use and outcomes in severe sepsis patients with and without pneumonia

PURPOSE Studies investigating the association between macrolides and outcomes in both pulmonary and nonpulmonary critically ill patients are limited. We aimed to examine the association between azithromycin use and clinical outcomes in severe sepsis patients with and without pneumonia receiving mechanical ventilation. MATERIALS AND METHODS A retrospective cohort of 105 patients admitted to an adult intensive care unit (ICU) with severe sepsis in an urban university hospital were included in the study. Multivariable linear regression was performed to assess the relationship between azithromycin use and the following outcomes: 28-day ICU-free days and 28-day ventilator-free days. RESULTS In univariate analysis, patients receiving azithromycin had nearly 6 more ICU-free days on average than did patients not receiving azithromycin (P = .005). The increased ICU-free days remained in multivariable analysis adjusting for age, sex, race, ICU type, and presence of shock (P = .005). In stratified analysis examining the association of azithromycin use in severe sepsis patients without pneumonia (n = 74), the results were similar to the full cohort. CONCLUSION Azithromycin was associated with more ICU-free days in severe sepsis patients with and without pneumonia. Further investigations are warranted to better elicit the association of macrolide use on clinical outcomes in severe sepsis patients, especially those without pneumonia.