Martin Tweeddale

Association of mortality with age of blood transfused in septic ICU patients

PurposeTo determine, retrospectively, the age of packed red blood cell (PRBC) units transfused to patients admitted to the ICU with the diagnosis of severe sepsis and to correlate this vanable with outcome.MethodsAll patients admitted to the ICU during 1992 with a diagnosis of severe sepsis were selected retrospectively. The criteria for the diagnosis of severe sepsis and septic shock were based on established guidelines. For each patient the total number of PRBC units transfused, the number of units transfused before, during and after the septic episode, and the age of each PRBC unit transfused were recorded.ResultsOf the 31 patients admitted to the ICU with severe sepsis, 19 died and 12 survived. No statistical differences between survivors and nonsurvivors were found with respect to age, sex, number of days in ICU, duration of sepsis, incidence of septic shock, admission Apache Il score or total number of PRBC units transfused. During sepsis the median age of PRBC units transfused to survivors was 17 days (range 5–35)vs 25 days (range 9–36) for nonsurvivors (P < 0.0001). A negative correlation (r = −0.73) was found between the proportion of PRBC units of a given age transfused to survivors and increasing age of PRBC.ConclusionThis is the first study to report a correlation of mortality with the age of PRBC transfused. The cause of this association is unclear. If this association is confirmed by a prospective randomised tnal it would have major implications for the use of PRBC in severe sepsis.RésuméObjectifDéterminer rétrospectivement l’âge des concentrés érythrocytaires (CE) transfusés à des patients admis à l’unité des soins intensifs (USI) avec un diagnostic de sepsis grave et vérifier si cette vanable a une corrélation avec le devenir des patients.MéthodesTous les patients admis à l’USI en 1992 avec un diagnostic de sepsis grave ont fait l’objet de cette recherche rétrospective. Les signes et symptômes usuels ont servi à établir les critères de sepsis grave et de choc septique. Pour chacun des patients la quantité totale des CE transfusés, le nombre de CE transfusés avant, pendant et après l’épisode septique et l’âge de chaque CE transfusé ont été enregistrés.RésultatsParmi les 31 patients admis à l’USI pour sepsis grave, 19 sont décédés et 12 ont survécu. Il n’y avait pas de différence statistique entre survivants et non survivants en rapport à l’âge, le sexe, la durée du séjour à l’USI, la durée du sepsis, l’incidence du choc septique, le score APACHE Il à l’admission et le nombre de CE transfusés. Au cours du sepsis, l’âge médian des CE transfusés était de 17 jours (écart 5–35)vs 25 jours (écart 9–39) pour les non survivants (P < 0,0001). On a trouvé une corrélation négative (r = −0,73) entre la proportion de CE d’un âge déterminé transfusé aux survivants et l’accroissement de l’âge des CE.ConclusionIl s’agit ici de la première étude concluant à une corrélation avec l’âge des CE transfusés. La raison de cette association n’est pas claire. Si une étude aléatoire prospective parvient à confirmer cette assertion, elle aurait des répercussions majeures sur la transfusion de CE dans le sepsis grave.

A Canadian survey of transfusion practices in critically ill patients

OBJECTIVES To characterize the contemporary red cell transfusion practice in the critically ill and to define clinical factors that influence these practices. DESIGN Scenario-based national survey. STUDY POPULATION Canadian critical care practitioners. MEASUREMENTS AND MAIN RESULTS We evaluated transfusion thresholds before transfusion and the number of red cell units ordered, under the given conditions. Of 254 Canadian critical care physicians, 193 (76%) responded to the survey. The primary specialty of most respondents was internal medicine (56%). Internal medicine respondents were in practice for an average of 8.4 +/- 5.7 (SD) yrs, and worked most often in combined medical/surgical intensive care units. Baseline hemoglobin transfusion thresholds averaged from 8.3 +/- 1.0 g/dL in a scenario involving a young stable trauma victim to 9.5 +/- 1.0 g/dL for an older patient after gastrointestinal bleeding. Transfusion thresholds differed significantly (p< .0001) between all four separate scenarios. With the exception of congestive heart failure (p> .05), all clinical factors (including age, Acute Physiology and Chronic Health Evaluation II score, preoperative status, hypoxemia, shock, lactic acidosis, coronary ischemia, and chronic anemia) significantly (p< .0001) modified the transfusion thresholds. A statistically significant (p< .01) difference in baseline transfusion thresholds was noted across four major regions (with a maximum of five academic centers per region) of the country. Low physician numbers in two of the regions did not allow for further investigation of regional variations. CONCLUSIONS There is significant variation in critical care transfusion practice, with many intensivists adhering to a 10.0-g/dL threshold, while other physicians described a much more restrictive approach to red cell transfusion. Also, many physicians opted to administer multiple units, despite published guidelines to the contrary. Additionally, the administration of red cells was strongly influenced by a number of clinical factors, many unique to intensive care unit patients. There is a need for prospective studies to define optimal practice in the critically ill.

Diastolic filling in human severe sepsis: an echocardiographic study.

OBJECTIVE To determine if nonsurvivors have a more abnormal pattern of left ventricular relaxation than survivors with severe sepsis. DESIGN Prospective, observational, cohort study. SETTING Intensive care unit in a university-affiliated tertiary care hospital. PATIENTS Twenty-four adults with severe sepsis. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Baseline clinical and hemodynamic variables, Acute Physiology and Chronic Health Evaluation (APACHE) II scores and Doppler echocardiographic mitral inflow pattern (analyzed for normalized peak early filling rate [E/VTI, systolic volumes/sec], deceleration time [msec], and early to atrial filling velocity ratio [E/A]). There were seven deaths. The patients did not differ in baseline demographics, inotropic infusions, hemodynamic measurements or ventilatory settings or variables. Nonsurvivors had a more abnormal pattern of left ventricular relaxation (E/VTI, 4.7 [range 3.8 to 5.8] vs. 5.8 [range 3.8 to 8.9], p= .04; deceleration time, 235 [range 209 to 367] vs. 182 [range 155 to 255], p = .002). E/A showed a nonsignificant trend in the same direction (0.9 [range 0.8 to 1.6] vs. 1.2 [range 0.7 to 1.9], p = .12). In a multivariate analysis, deceleration time (p< .004) and APACHE II score (p < .02) were the only independent predictors of mortality. CONCLUSION Severe sepsis nonsurvivors have a more abnormal echocardiographic pattern of left ventricular relaxation than survivors.

Severity of illness and risk of death associated with pulmonary artery catheter use

ObjectiveTo examine the association between the use of the pulmonary artery catheter and mortality rate in critically ill patients with a higher vs. a lower severity of illness. DesignObservational cohort study. SettingA tertiary care university teaching hospital from March 1988 to March 1998. PatientsA total of 7,310 critically ill adult patients. InterventionsNone. Measurements and Main ResultsThe main outcome measure was hospital mortality rate, controlled by multivariable logistic regression within four patient groups based on severity of illness. Cutoffs for severity of illness were chosen based on Acute Physiology and Chronic Health Evaluation (APACHE) II score 25th percentiles. Logistic regression analysis demonstrated no increased risk of death associated with exposure to the pulmonary artery catheter in the population as a whole. The associated odds ratio of hospital death for the entire cohort was 1.05 (95% confidence interval, 0.92–1.21). Subgroup analysis of severity of illness revealed the highest risk of death to be associated with the lowest APACHE II score quartile vs. a decreased associated mortality rate with the highest APACHE II score quartile after adjustment with multivariable logistic regression (APACHE II <18: odds ratio, 2.47, 95% confidence interval, 1.27–4.81; APACHE II 18–24: odds ratio, 1.64, 95% confidence interval, 1.24–2.17; APACHE II 25–31: odds ratio, 1.00, 95% confidence interval, 0.80–1.24; APACHE II >31: odds ratio, 0.80, 95% confidence interval, 0.64–1.00). ConclusionsThe use of the pulmonary artery catheter may decrease mortality rate in the most severely ill while increasing it in a population with a lower severity of illness. These findings underscore the necessity of examining the effect of severity of illness in future randomized controlled trials.

Transfusion requirements in critical care. A pilot study. Canadian Critical Care Trials Group.

OBJECTIVE To evaluate the effects of a restrictive and a liberal red blood cell (RBC) transfusion strategy on mortality and morbidity in critically ill patients. STUDY DESIGN Multicenter, prospective, randomized clinical trial. PATIENT POPULATION Sixty-nine normovolemic critically ill patients admitted to one of five tertiary level intensive care units with hemoglobin values less than 90 g/L within 72 hours of admission. INTERVENTIONS Patients were randomly allocated to one of two RBC transfusion strategies. Hemoglobin values were maintained between 100 and 120 g/L in the liberal transfusion group and between 70 and 90 g/L in the restrictive group. RESULTS Primary diagnosis and mean +/- SD age (58.6 +/- 15 vs 59.0 +/- 21 years and Acute Physiology and Chronic Health Evaluation II score (20 +/- 6.2 vs 21 +/- 7.2) were similar in the restrictive and liberal groups, respectively. Daily hemoglobin values averaged 90 g/L in the restrictive group vs 109 g/L in the liberal group (P < .001). The restrictive group received 2.5 U per patient compared with 4.8 U per patient in the liberal group. This represents a 48% relative decrease (P < .001) in RBC units transfused per patient. The 30-day mortality rate was 24% in the restrictive group compared with 25% in the liberal group; the 95% confidence interval around the absolute difference was -19% to 21%. Similar observations were noted for intensive care unit mortality (P = .76) and 120-day mortality (P > .99). In addition, survival analysis comparing time until death in both groups did not reveal any significant difference (P = .93) between groups. Organ dysfunction scores were also similar (P = .44). CONCLUSION In this small randomized trial, neither mortality nor the development of organ dysfunction was affected by the transfusion strategy, which suggests that a more restrictive approach to the transfusion of RBCs may be safe in critically ill patients. However, the study lacked power to detect small but clinically significant differences. Therefore, further investigations of RBC transfusion strategies are warranted.

DOES INCREASING OXYGEN DELIVERY IMPROVE OUTCOME IN THE CRITICALLY ILL? NO

The strategy of treating critically ill patients by increasing oxygen delivery and consumption to values previously observed among survivors of critical illness (supranormal values) is based on the belief that (1) tissue hypoxia may persist in critically ill patients despite aggressive early resuscitation to traditional endpoints of adequate tissue perfusion and (2) that increasing oxygen delivery can reverse tissue hypoxia. This article addresses the question of whether increasing oxygen delivery improves outcomes in critically ill patients by reviewing the relationship between whole-body oxygen delivery and consumption and by critically examining the randomized controlled trials that have increased oxygen delivery to supranormal values.