David R. Gerber

Transfusion of packed red blood cells in patients with ischemic heart disease

Objective:To review the current literature concerning the utility of and complications associated with transfusion of packed red blood cells (PRBC) in medical and surgical patients with ischemic heart disease. Data Sources, Study Selection, and Data Extraction:The PubMed database of the National Library of Medicine was searched for all studies investigating the use of PRBC in medical and surgical patients with cardiac disease published since 1999. Relevant background literature from before that date was reviewed for inclusion as well. Data Synthesis:An extensive body of literature has accumulated evaluating the safety and efficacy of transfusion as a therapeutic modality in a wide variety of critically ill patients, including patients with cardiac disease. Most, but not all, of these studies have been retrospective in nature, and methodologies have varied from study to study. Some have involved retrospective reviews of patient records, some have been retrospective analyses of detailed databases prospectively collected for other purposes, and some have been prospective randomized or observational studies. Despite the variability in data sources and study design, with a handful of exceptions, the preponderance of data indicates that transfusion of PRBC in the population of patients with ischemic heart disease is of limited clinical utility and may carry the potential for serious adverse consequences. Conclusions:Based on the current literature, there appears to be no indication for routine transfusion in patients with non-ST-elevation acute coronary syndrome, although anemic patients with ST-elevation myocardial infarction may benefit from this intervention. However, the specific indications for transfusion in this population remain ill-defined.

Clinical characteristics and outcomes of septic patients with new-onset atrial fibrillation

PURPOSE No studies have specifically evaluated the incidence or clinical characteristics of atrial fibrillation (AF) in a mixed medical-surgical population of patients with sepsis. We undertook to determine the incidence and clinical course of critically ill septic patients in the intensive care unit (ICU) who developed new-onset AF. METHODS Retrospective analysis of data collected from the Project IMPACT database on 274 septic patients from July 2003 to December 2004. RESULTS Sixteen evaluable septic patients with new-onset AF were identified. Mortality was higher (P = .034) and ICU length of stay (LOS) longer (P = .003) in patients with AF vs those without. Intensive care unit LOS was also longer in the subset of survivors with AF (P = .0001). Hospital LOS was longer among survivors with AF than in survivors without AF (P = .047). Patients with AF had a greater need for mechanical ventilation (P = .0007). Survivors with AF had longer duration of mechanical ventilation than those without AF (P = .006). CONCLUSIONS Statistically significantly higher mortality was observed in critically ill septic patients with new-onset AF, as were longer duration of mechanical ventilation, ICU, and hospital LOS. Whether the higher incidence of AF in septic patients is a specific risk factor for outcome or an indication of severity of illness remains to be determined.

Dexmedetomidine Infusion as Adjunctive Therapy to Benzodiazepines for Acute Alcohol Withdrawal

Objective: To report a case of alcohol withdrawal and delirium tremens successfully treated with adjunctive dexmedetomidine. Case Summary: A 30–year-old man with a history of alcohol abuse was admitted to the general medical unit because of altered mental status and agitation. He was initially treated for alcohol withdrawal with benzodiazepines; his condition then deteriorated and he was transferred to the intensive care unit. Because of the patients poor response to benzodiazepines (oxazepam and lorazepam, with midazolam the last one used), intravenous dexmedetomidine was started at an initial dose of 0.2 µg/kg/h and titrated to 0.7 µg/kg/h to the patients comfort. Midazolam was subsequently tapered to discontinuation due to excessive sedation. In the intensive care unit, the patients symptoms remained controlled with use of dexmedetomidine alone. He remained in the intensive care unit for 40 hours; dexmedetomidine was then tapered to discontinuation and the patient was transferred back to the general medical unit on oral oxazepam and thiamine, which had been started in the emergency department. He was discharged after 5 days. Discussion: A review of the PubMed database (1989-2007} failed to identify any other instances of dexmedetomidine having been used as the principal agent to treat alcohol withdrawal. The use of sedative to treat delirium tremens Is well documented, with benzodiazepines being the agents of choice. The clinical utility of benzodiazepines is limited by their stimulation of the γ-aminobutyric acid receptors, an effect not shared by dexmedetomidine, a central α2-receptor agonist that induces a state of cooperative sedation and does not suppress respiratory drive. Conclusions: In patients with delirium tremens, dexmedetomidine should be considered as an option for primary treatment. This case illustrates the need for further studies to investigate other potential uses for dexmedetomidine.

Transfusion of packed red blood cells is not associated with improved central venous oxygen saturation or organ function in patients with septic shock.

BACKGROUND The exact role of packed red blood cell (PRBC) transfusion in the setting of early resuscitation in septic shock is unknown. STUDY OBJECTIVE To evaluate whether PRBC transfusion is associated with improved central venous oxygen saturation (ScvO(2)) or organ function in patients with severe sepsis and septic shock receiving early goal-directed therapy (EGDT). METHODS Retrospective cohort study (n=93) of patients presenting with severe sepsis or septic shock treated with EGDT. RESULTS Thirty-four of 93 patients received at least one PRBC transfusion. The ScvO(2) goal>70% was achieved in 71.9% of the PRBC group and 66.1% of the no-PRBC group (p=0.30). There was no difference in the change in Sequential Organ Failure Assessment (SOFA) score within the first 24 h in the PRBC group vs. the no-PRBC group (8.6-8.3 vs. 5.8-5.6, p=0.85), time to achievement of central venous pressure>8 mm Hg (732 min vs. 465 min, p=0.14), or the use of norepinephrine to maintain mean arterial pressure>65 mm Hg (81.3% vs. 83.8%, p=0.77). CONCLUSIONS In this study, the transfusion of PRBC was not associated with improved cellular oxygenation, as demonstrated by a lack of improved achievement of ScvO(2)>70%. Also, the transfusion of PRBC was not associated with improved organ function or improved achievement of the other goals of EGDT. Further studies are needed to determine the impact of transfusion of PRBC within the context of early resuscitation of patients with septic shock.

The impact of packed red blood cell transfusion on clinical outcomes in patients with septic shock treated with early goal directed therapy.

Background: The optimal hemoglobin level and transfusion threshold in patients with septic shock treated with an early, goal oriented approach to resuscitation remains unknown. Aims: To assess the impact of packed red blood cell (PRBC) transfusion on clinically relevant outcomes in patients with septic shock treated with early goal directed therapy (EGDT). Settings and Design: Retrospective cohort study of 93 patients who presented with septic shock, to a single center academic intensive care unit and received EGDT. Materials and Methods: Data were collected on patients identified via the Surviving Sepsis Campaign Chart Review database and linked to Project IMPACT database. The PRBC group and no PRBC group were compared by the Pearson chi-square and Fisher’s exact test to analyze statistical significance. Results: The PRBC group had a mortality of 41.2% vs. 33.9% in the no PRBC transfusion group (P = NS). The PRBC group also had more mechanical ventilation days (11.2 days vs. 5.0 days, (P ≤ 0.05), longer hospital length of stay (25.9 days vs. 12.5 days, (P ≤ 0.05), and longer intensive care unit length of stay (11.4 days vs. 3.8 days, (P ≤ 0.05). Conclusions: In this retrospective cohort study, transfusion of PRBCs was associated with worsened clinical outcomes in patients with septic shock treated with EGDT. Further studies are needed to determine the impact of transfusion of PRBC within the context of early resuscitation of patients with septic shock, as the beneficial effects gained by an early and goal oriented approach to resuscitation may be lost by the negative effects associated with PRBC transfusion.

Anemia and Blood Transfusions in Critically Ill Patients

Anemia is common in critically ill patients. As a consequence packed red blood cell (PRBC) transfusions are frequent in the critically ill. Over the past two decades a growing body of literature has emerged, linking PRBC transfusion to infections, immunosuppression, organ dysfunction, and a higher mortality rate. However, despite growing evidence that risk of PRBC transfusion outweighs its benefit, significant numbers of critically ill patients still receive PRBC transfusion during their intensive care unit (ICU) stay. In this paper, we summarize the current literature concerning the impact of anemia on outcomes in critically ill patients and the potential complications of PRBC transfusions.

Risks of packed red blood cell transfusion in patients undergoing cardiac surgery

Packed red blood cell (PRBC) transfusion is common in patients undergoing cardiac surgery. Evidence has accumulated demonstrating that such patients can tolerate relatively low hemoglobins, and an extensive body of literature has developed demonstrating that patients undergoing such surgery who receive PRBC are at risk for several adverse outcomes including increased mortality, atrial fibrillation, and more postoperative infections, as well as numerous other complications. The PubMed database was searched for the English language literature on the topic of PRBC transfusion and outcomes in patients undergoing cardiac surgery, as well as alternatives to this intervention. Data were reviewed to assess the impact of transfusion in patients undergoing cardiac surgery on mortality, cardiac, infectious, and pulmonary, as well as a variety of miscellaneous complications. Patients receiving PRBC were consistently identified as being at higher risk for complications in all categories. The limited prospective data were consistent with the retrospective data, which comprised most of the literature. The preponderance of the literature suggests that patients undergoing cardiac surgery can tolerate lower hemoglobin/hematocrit values than traditionally appreciated. Most published data also indicate that PRBC transfusion should be reserved for patients with an identifiable clinical/physiologic indication fir this intervention, consistent with recent specialty society guidelines.

Association between out-of-hospital emergency department transfer and poor hospital outcome in critically ill stroke patients

INTRODUCTION Transfer of critically ill patients from outside emergency department has the potential for delaying the admission to the intensive care unit. We sought to determine the effect of outside emergency department transfer on hospital outcomes in critically ill patients with stroke. METHODS We designed a retrospective cohort analysis using a prospectively compiled and maintained registry (Cerner Project IMPACT). Patients with acute ischemic stroke and intracerebral hemorrhage admitted to our intensive care unit from our emergency department and transfers from outside emergency department within 24 hours of stroke between January 1, 2003, and December 31, 2008, were selected for the analysis. Data collected included demographics, admission physiologic variables, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation II score, and total intensive care unit and hospital length of stay. Primary (poor) outcome was a composite of death or fully dependent status at hospital discharge, and secondary outcomes were intensive care unit and hospital length of stay. To assess for the impact of outside emergency department transfer on primary and secondary outcomes, demographic and admission clinical variables were used to construct logistic regression models using the outcome measure as a dependent variable. RESULTS A total of 448 patients were selected for analysis. The mean age was 65 ± 14 years, of which 214 (48%) were male and 282 (65%) white, 152 (34%) were patients with acute ischemic stroke, and 296 (66%) were patients with intracerebral hemorrhage. The median hospital length of stay was 7 days (interquartile range, 4-11 days) and median intensive care unit length of stay was 2 days (interquartile range, 1-3 days). Overall hospital mortality was 30%, and outside emergency department transfer increased the odds of poor outcome by 2-fold (65% vs 34%; P = .05). Multivariate regression analysis showed that age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.01-1.1), Acute Physiology and Chronic Health Evaluation II score >14 (OR, 1.9; 95% CI, 1.3-2.7), Glasgow Coma Scale <12 (OR, 2.0; 95% CI, 1.4-2.8), do-not-resuscitate status (OR, 3.5; 95% CI, 2.2-5.9), and outside emergency department transfers (OR, 1.4; 95% CI, 1.02-1.8) were independently associated with poor outcome. Outside emergency department transfer was not significantly associated with secondary outcomes. CONCLUSION These data suggest that in critically ill patients with stroke, transfer from outside emergency department is independently associated with poor outcome at hospital discharge. Further research is needed as to identify the potential causes for this effect.

Acute Respiratory Failure with a Single Dose of Quetiapine Fumarate

Objective: To report a case of acute respiratory failure after a single dose of quetiapine fumarate in an elderly patient with a history of chronic obstructive pulmonary disease (COPD). Case Summary: A 92-year-old woman with a history of COPD was admitted to the hospital with pneumonia. Her symptoms improved with antibiotics. Because of acute agitation and delirium, quetiapine 50 mg twice daily was started. After receiving the first dose, the woman developed acute respiratory failure and severe central nervous system depression. She required mechanical ventilation and supportive care in the intensive care unit (ICU). She had a full recovery within 24 hours. Discussion: Quetiapine is an atypical antipsychotic that has been used successfully for the treatment of schizophrenia and bipolar disorder for many years. Recently, it has also been used to treat delirium and agitation. It has proven to be very safe, even in the elderly. In previously reported cases, serious adverse effects were seen in patients who ingested very high doses of quetiapine. Those patients required intubation and supportive care in the ICU. To our knowledge, as of January 19, 2006, this is the first case report of acute respiratory failure of such severity with one dose of quetiapine. Using the Naranjo probability scale, we conclude that the acute respiratory failure observed in this patient was probably related to quetiapine. Conclusions: This case suggests that quetiapine can have significant adverse effects even with a single 50 mg dose. Elderly patients, especially those with significant underlying pulmonary pathology, should be monitored closely when started on this medication.

Prevalence and impact of anemia in hospitalized patients.

Objective The prevalence of anemia is increasing in the general population similarly to other comorbidities and is associated with high mortality in a variety of settings. Most studies, however, have analyzed older adults or specific comorbidities, and the independent impact of anemia on outcomes in a general population of hospitalized patients has not been clearly defined. Methods Retrospective analysis of a medical records database of all consecutive patient discharges (aged 18 years or older) admitted to our institution from January 1, 1999 through December 31, 2008. Results A total of 179,516 admissions were included. Of these, 18,589 patients were diagnosed as having anemia (10.4%). There were 123,586 patients younger than 65 years. The prevalence of anemia among all of the discharges was characterized by a significant linear increase across the 10-year time frame, from 8.7% (1999) to 12.8% (2008), as was the average number of comorbidities. Over time, anemic patients were characterized by increasing comorbidity. Anemia was significantly associated with mortality (6.5% vs 2.5%; P < 0.001, odds ratio 2.68). This association remained significant after additional adjustment for demographic characteristics and comorbidities. The risk of mortality was significantly higher in patients younger than 65 years than it was in patients older than 65 (odds ratio 3.2 vs 2.1, respectively). Conclusions The prevalence of anemia increased during a 10-year time frame, as did the average number of associated comorbid conditions. With adjustment for time, demographic factors, and additional comorbidities, anemia remained independently associated with mortality. This association was stronger in younger patients.