Jeffrey L. Carson

The Clinical Course of Pulmonary Embolism

BACKGROUND Pulmonary embolism is a potentially fatal disorder. Information about the outcome of clinically recognized pulmonary embolism is sparse, particularly given that new treatments for more seriously ill patients are now available. METHODS We prospectively followed 399 patients with pulmonary embolism diagnosed by lung scanning and pulmonary angiography, who were enrolled in a multicenter diagnostic trial. We reviewed all hospitalizations, all new investigations of pulmonary embolism, and all deaths among the patients within one year of diagnosis. RESULTS Of the 399 patients, 375 (94 percent) received treatment for pulmonary embolism, usually conventional anticoagulation. Only 10 patients (2.5 percent) died of pulmonary embolism; 9 of them had clinically suspected recurrent pulmonary embolism. Clinically apparent pulmonary embolism recurred in 33 patients (8.3 percent), of whom 45 percent died during follow-up. Ninety-five patients with pulmonary embolism (23.8 percent) died within one year. The conditions associated with these deaths were cancer (relative risk, 3.8; 95 percent confidence interval, 2.3 to 6.4), left-sided congestive heart failure (relative risk, 2.7; 95 percent confidence interval, 1.5 to 4.6), and chronic lung disease (relative risk, 2.2; 95 percent confidence interval, 1.2 to 4.0). The most frequent causes of death in patients with pulmonary embolism were cancer (in 34.7 percent), infection (22.1 percent), and cardiac disease (16.8 percent). CONCLUSIONS When properly diagnosed and treated, clinically apparent pulmonary embolism was an uncommon cause of death, and it recurred in only a small minority of patients. Most deaths were due to underlying diseases. Patients with pulmonary embolism who had cancer, congestive heart failure, or chronic lung disease had a higher risk of dying within one year than did other patients with pulmonary embolism.

Effect of anaemia and cardiovascular disease on surgical mortality and morbidity.

BACKGROUND Guidelines have been offered on haemoglobin thresholds for blood transfusion in surgical patients. However, good evidence is lacking on the haemoglobin concentrations at which the risk of death or serious morbidity begins to rise and at which transfusion is indicated. METHODS A retrospective cohort study was performed in 1958 patients, 18 years and older, who underwent surgery and declined blood transfusion for religious reasons. The primary outcome was 30-day mortality and the secondary outcome was 30-day mortality or in-hospital 30-day morbidity. Cardiovascular disease was defined as a history of angina, myocardial infarction, congestive heart failure, or peripheral vascular disease. FINDINGS The 30-day mortality was 3.2% (95% CI 2.4-4.0). The mortality was 1.3% (0.8-2.0) in patients with preoperative haemoglobin 12 g/dL or greater and 33.3% (18.6-51.0) in patients with preoperative haemoglobin less than 6 g/dL. The increase in risk of death associated with low preoperative haemoglobin was more pronounced in patients with cardiovascular disease than in patients without (interaction p < 0.03). The effect of blood loss on mortality was larger in patients with low preoperative haemoglobin than in those with a higher preoperative haemoglobin (interaction p < 0.001). The results were similar in analyses of postoperative haemoglobin and 30-day mortality or in-hospital morbidity. INTERPRETATION A low preoperative haemoglobin or a substantial operative blood loss increases the risk of death or serious morbidity more in patients with cardiovascular disease than in those without. Decisions about transfusion should take account of cardiovascular status and operative blood loss as well as the haemoglobin concentration.

Liberal or Restrictive Transfusion in High-Risk Patients after Hip Surgery

BACKGROUND The hemoglobin threshold at which postoperative red-cell transfusion is warranted is controversial. We conducted a randomized trial to determine whether a higher threshold for blood transfusion would improve recovery in patients who had undergone surgery for hip fracture. METHODS We enrolled 2016 patients who were 50 years of age or older, who had either a history of or risk factors for cardiovascular disease, and whose hemoglobin level was below 10 g per deciliter after hip-fracture surgery. We randomly assigned patients to a liberal transfusion strategy (a hemoglobin threshold of 10 g per deciliter) or a restrictive transfusion strategy (symptoms of anemia or at physician discretion for a hemoglobin level of <8 g per deciliter). The primary outcome was death or an inability to walk across a room without human assistance on 60-day follow-up. RESULTS A median of 2 units of red cells were transfused in the liberal-strategy group and none in the restrictive-strategy group. The rates of the primary outcome were 35.2% in the liberal-strategy group and 34.7% in the restrictive-strategy group (odds ratio in the liberal-strategy group, 1.01; 95% confidence interval [CI], 0.84 to 1.22), for an absolute risk difference of 0.5 percentage points (95% CI, -3.7 to 4.7). The rates of in-hospital acute coronary syndrome or death were 4.3% and 5.2%, respectively (absolute risk difference, -0.9%; 99% CI, -3.3 to 1.6), and rates of death on 60-day follow-up were 7.6% and 6.6%, respectively (absolute risk difference, 1.0%; 99% CI, -1.9 to 4.0). The rates of other complications were similar in the two groups. CONCLUSIONS A liberal transfusion strategy, as compared with a restrictive strategy, did not reduce rates of death or inability to walk independently on 60-day follow-up or reduce in-hospital morbidity in elderly patients at high cardiovascular risk. (Funded by the National Heart, Lung, and Blood Institute; FOCUS ClinicalTrials.gov number, NCT00071032.).

Red blood cell transfusion: A Clinical practice guideline from the AABB

DESCRIPTION Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children. METHODS These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay. RECOMMENDATION 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence). RECOMMENDATION 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence). RECOMMENDATION 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).

Mortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion.

BACKGROUND: Guidelines for allogeneic transfusion emphasize minimizing use to avoid transmission of serious illness. However, there is little information on the risks associated from withholding transfusion.

Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery

OBJECTIVES The aim of this study was to determine the impact of diabetes mellitus (DM) on short-term mortality and morbidity in patients undergoing coronary artery bypass surgery (CABG). BACKGROUND Diabetes mellitus is present in approximately 20% to 30% of patients undergoing CABG, and the impact of diabetes on short-term outcome is unclear. METHODS We performed a retrospective cohort study in 434 hospitals from North America. The study population included 146,786 patients undergoing CABG during 1997: 41,663 patients with DM and 105,123 without DM. The primary outcome was 30-day mortality. Secondary outcomes were in-hospital morbidity, infections and composite outcomes of mortality or morbidity and mortality or infection. RESULTS The 30-day mortality was 3.7% in patients with DM and 2.7% in those without DM; the unadjusted odds ratio was 1.40 (95% confidence interval [CI], 1.31 to 1.49). After adjusting for other baseline risk factors, the overall adjusted odds ratio for diabetics was 1.23 (95% CI, 1.15 to 1.32). Patients treated with oral hypoglycemic medications had adjusted odds ratio 1.13; 95% CI, 1.04 to 1.23, whereas those on insulin had an adjusted odds ratio 1.39; 95% CI, 1.27 to 1.52. Morbidity, infections and the composite outcomes occurred more commonly in diabetic patients and were associated with an adjusted risk about 35% higher in diabetics than nondiabetics, particularly among insulin-treated diabetics (adjusted risk between 1.5 to 1.61). CONCLUSIONS Diabetes mellitus is an important risk factor for mortality and morbidity among those undergoing CABG. Research is needed to determine if good control of glucose levels during the perioperative time period improves outcome.

Red blood cell transfusion in clinical practice

Every year, about 75 million units of blood are collected worldwide. Red blood cell (RBC) transfusion is one of the few treatments that adequately restore tissue oxygenation when oxygen demand exceeds supply. Although the respiratory function of blood has been studied intensively, the trigger for RBC transfusion remains controversial, and doctors rely primarily on clinical experience. Laboratory assays that indicate failing tissue oxygenation would be ideal to guide the need for transfusion, but none has proved easy, reproducible, and sensitive to regional tissue hypoxia. The clinical importance of the RBCs storage lesion (ie, the time-dependent metabolic, biochemical, and molecular changes that stored blood cells undergo) is poorly understood. RBCs can be filtered, washed, frozen, or irradiated for specific indications. Donor screening and testing have dramatically reduced infectious risks in the developed world, but infection remains a major hazard in developing countries, where 13 million units of blood are not tested for HIV or hepatitis viruses. Pathogen inactivation techniques are in clinical trials for RBCs, but none is available for use. Despite serious immunological and non-immunological complications, RBC transfusion holds a therapeutic index that exceeds that of many common medications.

SEVERITY OF ANAEMIA AND OPERATIVE MORTALITY AND MORBIDITY

In a case-control study of 125 surgical patients who declined blood transfusions for religious reasons operative mortality was inversely related to the preoperative haemoglobin level, rising from 7.1% for patients with levels above 10 g/dl to 61.5% for those with levels below 6 g/dl. Mortality rates were also related to blood loss during surgery, rising from 8% for patients who lost less than 500 ml to 42.9% for those who lost more than 2000 ml. Both preoperative haemoglobin level and operative blood loss should be considered in assessing the need for preoperative transfusion. In our study no patient with a haemoglobin level above 8 g/dl and operative blood loss below 500 ml died.

Risk of bacterial infection associated with allogeneic blood transfusion among patients undergoing hip fracture repair.

BACKGROUND: The relationship between allogeneic blood transfusion and bacterial infection remains uncertain. An increased risk of bacterial infection would represent the most important risk of allogeneic transfusion, because viral disease transmission has become so rare.

Effects of Red-Cell Storage Duration on Patients Undergoing Cardiac Surgery

BACKGROUND Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. METHODS We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. RESULTS The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. CONCLUSIONS The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).