Richard B. Weiskopf

Transfusion related acute lung injury: incidence and risk factors

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current smoking, and positive fluid balance. Transfusion risk factors were receipt of plasma or whole blood from female donors (odds ratio = 4.5, 95% confidence interval [CI], 1.85-11.2, P = .001), volume of HLA class II antibody with normalized background ratio more than 27.5 (OR = 1.92/100 mL, 95% CI, 1.08-3.4, P = .03), and volume of anti-human neutrophil antigen positive by granulocyte immunofluoresence test (OR = 1.71/100 mL, 95% CI, 1.18-2.5, P = .004). Little or no risk was associated with older red blood cell units, noncognate or weak cognate class II antibody, or class I antibody. Reduced transfusion of plasma from female donors was concurrent with reduced TRALI incidence: 2.57 (95% CI, 1.72-3.86) in 2006 versus 0.81 (95% CI, 0.44-1.49) in 2009 per 10 000 transfused units (P = .002). The identified risk factors provide potential targets for reducing residual TRALI.

What can we learn about the need for transfusion from patients who refuse blood? The experience with Jehovah's Witnesses

BACKGROUND: A transfusion threshold of 7 g per dL (70 g/L) of hemoglobin has been proposed for patients, although scant human data are available to support this recommendation.

Kinetics of desflurane, isoflurane, and halothane in humans.

The low solubility of desflurane in blood and tissues suggests that the partial pressures of this agent in blood and tissues should approach the inspired partial pressure more rapidly than would the blood and tissue partial pressures of other potent inhaled anesthetics. We tested this prediction, comparing the pharmacokinetics of desflurane with those of isoflurane, halothane, and nitrous oxide in eight volunteers. We measured the rate at which the alveolar (endtidal) (FA) concentration of nitrous oxide increased towards an inspired (FI) concentration of 65-70%, and then measured the concurrent increase in FA and mixed expired concentrations (FM) of desflurane, isoflurane, and halothane at respective FI values of 2.0%, 0.4%, 0.2%. Minute ventilation (VE) was measured concurrently with the measurements of anesthetic concentrations. The potent vapors were administered for 30 min; administration of nitrous oxide continued throughout the period of anesthesia. For the potent agents, we also measured VE, FA, and FM for 5-7 days of elimination. We used FA/FI and FA/FA0 (FA0 = the last FA during the administration of each anesthetic) to define the rate of increase of anesthetic in the lungs and the rate of elimination of anesthetic, respectively. FA/FI values at 30 min of administration were: (mean +/- SD) nitrous oxide 0.99 +/- 0.01, desflurane 0.90 +/- 0.01, isoflurane 0.73 +/- 0.03, and halothane 0.58 +/- 0.04. FA/FA0 values after 5 min of elimination were: desflurane 0.14 +/- 0.02, isoflurane 0.22 +/- 0.02, and halothane 0.25 +/- 0.02. Recovery (volume of anesthetic recovered during elimination per volume taken up) of desflurane (105 +/- 25%) equalled recovery of isoflurane (102 +/- 13%) and exceeded recovery of halothane (64 +/- 9%). Time constants for a five-compartment mammillary model for halothane and isoflurane differed for the lungs, fat group, and hepatic metabolism, and exceeded those for desflurane for all compartments. In summary, we found that FA/FI of desflurane increases more rapidly and that FA/FA0 decreases more rapidly in humans than do these variables with other available potent anesthetics. We also found that desflurane resists biodegradation in humans and so may have little or no toxic potential.

Acute severe isovolemic anemia impairs cognitive function and memory in humans.

Background Erythrocytes are transfused to prevent or treat inadequate oxygen delivery resulting from insufficient hemoglobin concentration. Previous studies failed to find evidence of inadequate systemic oxygen delivery at a hemoglobin concentration of 5 g/dl. However, in those studies, sensitive, specific measures of critical organ function were not used. This study tested the hypothesis that acute severe decreases of hemoglobin concentration alters human cognitive function. Methods Nine healthy volunteers, age 29 ± 5 yr (mean ± SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and after acute isovolemic reduction of their hemoglobin to 7, 6, and 5 g/dl and again after transfusion of their autologous erythrocytes to return their hemoglobin concentration to 7 g/dl. To control for duration of the experiment, each volunteer also completed the same tests on a separate day, without alteration of hemoglobin, at times of the day approximately equivalent to those on the experimental day. Results No test showed any change in reaction time or error rate at hemoglobin concentration of 7 g/dl compared with the data at the baseline hemoglobin concentration of 14 g/dl. Reaction time, but not error rate, for horizontal addition and digit–symbol substitution test (DSST) increased at hemoglobin 6 g/dl (mean horizontal addition, 19%; 95% confidence interval [CI], 4–34%; mean DSST, 10%; 95% CI, 4–17%) and further at 5 g/dl (mean horizontal addition, 43%; 95% CI, 6–79%; mean DSST, 18%; 95% CI, 4–31%). Immediate and delayed memory was degraded at hemoglobin 5 g/dl but not at 6 g/dl. Return of hemoglobin to 7 g/dl returned all tests to baseline, except for the DSST, which significantly improved, and returned to baseline the following morning after transfusion of all autologous erythrocytes. Conclusion Acute reduction of hemoglobin concentration to 7 g/dl does not produce detectable changes in human cognitive function. Further reduction of hemoglobin level to 6 and 5 g/dl produces subtle, reversible increases in reaction time and impaired immediate and delayed memory. These are the first prospective data to demonstrate subtle degraded human function with acute anemia of hemoglobin concentrations of 6 and 5 g/dl. This reversibility of these decrements with erythrocyte transfusion suggests that our model can be used to test the efficacy of erythrocytes, oxygen therapeutics, or other treatments for acute anemia.

Comparison of kinetics of sevoflurane and isoflurane in humans.

The low solubility of sevoflurane in blood suggests that this agent should enter and leave the body more rapidly than isoflurane. However, the closeness of sevoflurane and isoflurane tissue/blood partition coefficients suggests that the rates of equilibration with and elimination from tissues should be similar. We tested both predictions, comparing sevoflurane with isoflurane and nitrous oxide in seven volunteers. We measured the rate at which the alveolar (end-tidal) (FA) concentration of nitrous oxide increased toward an inspired (FI) concentration of 65%–70%, then measured the concurrent rise in FA and mixed expired concentrations (FM) of sevoflurane and isoflurane at respective FI values of 1.0% sevoflurane and 0.6% isoflurane for 30 min. Minute ventilation (V E) was measured concurrently with the measurements of anesthetic concentrations. For the potent agents, we also measured V E, FA and FM for 6–7 days of elimination. FA/FI values at 30 min of administration were as follows: nitrous oxide, 0.986 ± 0.003 (mean ± SD); sevoflurane, 0.850 ± 0.018; and isoflurane, 0.733 ± 0.027. FA/FA0 (FA0 = the last FA during administration) values after 5 min of elimination were as follows: sevoflurane, 0.157 ± 0.020; isoflurane, 0.223 ± 0.024. Recovery (volume of anesthetic recovered during elimination/volume taken up) of sevoflurane (101% ± 7%) equaled recovery of isoflurane (101% ± 6%). Time constants for a five-compartment mammillary model for sevoflurane were smaller than those for isoflurane for the lungs but were not different from isoflurane for the other compartments. In summary, we found (a) that FA/FI of sevoflurane increases and FA/FA0 decreases more rapidly than do these variables with isoflurane in humans; but (b) that elimination from tissues did not differ between sevoflurane and isoflurane; and (c) that the metabolism of sevoflurane did not differ from that estimated for isoflurane.

Clinical characteristics of desflurane in surgical patients : minimum alveolar concentration

Desflurane (formerly I-653) is a new inhalaticnal anesthetic with a promising pharmacokinetic profile that includes low solubility in blood and tissue, including fat. Since its lipid solubility is less than that of other volatile agents, it may have lower potency. Low solubility would be expected to increase the rate at which alveolar concentration approaches inspired concentration during induction as well as to increase the rate of elimination of desflurane from blood at emergence. We determined the minimum alveolar concentration (MAC) of desflurane in 44 unpremedicated ASA physical status 1 or 2 patients undergoing elective surgery. We prospectively studied four patient groups distinguished by age and anesthetic regimen: 18-30 versus 31-65 yr and desflurane in 60% N2O/40% O2 versus desflurane in O2. Anesthesia was induced with desflurane or desflurane in 60% N2O/40% O2. MAC was determined by a modification of Dixons up-and-down method with increments of 0.5% desflurane. The MAC of desflurane in O2 was 7.25 +/- 0.0 (mean +/- SD) in the 18-30-yr age group, and 6.0 +/- 0.29 in the 31-65-yr group; the addition of 60% N2O reduced the MAC to 4.0 +/- 0.29 and 2.83 +/- 0.58, respectively. The median time from discontinuation of desflurane to an appropriate response to commands was 5.25 min. Desflurane appears to be a mild airway irritant but was well tolerated by all patients.

Awareness during anesthesia.

To the Editor: All anesthesiologists will join me in extending sincere sympathy to Ms. Hoogewerf, who was aware during surgery for an ovarian cyst (Can J Anaesth 1998; 45: 821). This mishap is one of the twenty sudden occurrences which anesthesiologists most dread while they administer anesthesia. Though very rare, some physicians become so fearful of encountering such an event that they withdraw from the practice of anesthesia. However, Ms. Hoogewerf makes the very important point that the administration of anesthesia is very difficult, and fraught with uncertainty, because we are not dealing with predictable programmable inanimate objects, but are anesthetizing people, whose condition may change with startling rapidity. This morning I anesthetized two consecutive patients: the first required only 20% of the expected quantity of anesthetic agent and recovered within 20 mins while the family asked three times why recovery was so slow. The second patient required 100% more anesthesia than the average patient, but was adequately anesthetized and recovered normally. We should all be grateful to your correspondent for highlighting the problems of providing anesthesia, and resolve to be aware of the difficulties and the possibility of awareness during light anesthesia.

Critical Oxygen Delivery in Conscious Humans Is Less Than 7.3 ml O2· kg−1· min−1

Background The “critical” level of oxygen delivery (DO2) is the value below which DO2 fails to satisfy the metabolic need for oxygen. No prospective data in healthy, conscious humans define this value. The authors reduced DO2 in healthy volunteers in an attempt to determine the critical DO2. Methods With Institutional Review Board approval and informed consent, the authors studied eight healthy, conscious volunteers, aged 19–25 yr. Hemodynamic measurements were obtained at steady state before and after profound acute isovolemic hemodilution with 5% albumin and autologous plasma, and again at the reduced hemoglobin concentration after additional reduction of DO2 by an infusion of a &bgr;-adrenergic antagonist, esmolol. Results Reduction of hemoglobin from 12.5 ± 0.8 g/dl to 4.8 ± 0.2 g/dl (mean ± SD) increased heart rate, stroke volume index, and cardiac index, and reduced DO2 (14.0 ± 2.9 to 9.9 ± 2.0 ml O2 · kg−1 · min−1; all P < 0.001). Oxygen consumption (VO2; 3.0 ± 0.5 to 3.4 ± 0.6 ml O2 · kg−1 · min−1;P < 0.05) and plasma lactate concentration (0.50 ± 0.10 to 0.62 ± 0.16 mM;P < 0.05; n = 7) increased slightly. Esmolol decreased heart rate, stroke volume index, and cardiac index, and further decreased DO2 (to 7.3 ± 1.4 ml O2 · kg−1 · min−1; all P < 0.01 vs. before esmolol). VO2 (3.2 ± 0.6 ml O2 · kg−1 · min−1;P > 0.05) and plasma lactate (0.66 ± 0.14 mM;P > 0.05) did not change further. No value of plasma lactate exceeded the normal range. Conclusions A decrease in DO2 to 7.3 ± 1.4 ml O2 · kg−1 · min−1 in resting, healthy, conscious humans does not produce evidence of inadequate systemic oxygenation. The critical DO2 in healthy, resting, conscious humans appears to be less than this value.

Safety of Modern Starches Used During Surgery

Various hydroxyethyl starch (HES) preparations have been used for decades to augment blood volume. There has been concern recently regarding possible adverse outcomes when using HES in the intensive care setting, especially in patients with septic shock. However, the pharmacokinetic and pharmacodynamic properties of HES preparations depend on their chemical composition and source material. Thus, different clinical conditions could result in differing effectiveness and safety for these preparations. Consequently, we assessed the safety of tetrastarches when used during surgery, using a formal search, that yielded 59 primary full publications of studies that met a priori inclusion criteria and randomly allocated 4529 patients with 2139 patients treated with tetrastarch compared with 2390 patients treated with a comparator. There were no indications that the use of tetrastarches during surgery induces adverse renal effects as assessed by change or absolute concentrations of serum creatinine or need for renal replacement therapy (39 trials, 3389 patients), increased blood loss (38 trials, 3280 patients), allogeneic erythrocyte transfusion (20 trials, 2151 patients; odds ratio for HES transfusion 0.73 [95% confidence interval = 0.61–0.87], P = 0.0005), or increased mortality (odds ratio for HES mortality = 0.51 [0.24–1.05], P = 0.079).

Fresh Blood and Aged Stored Blood Are Equally Efficacious in Immediately Reversing Anemia-induced Brain Oxygenation Deficits in Humans

Background:Erythrocytes are transfused to treat or prevent imminent inadequate tissue oxygenation. 2,3-diphosphoglycerate concentration decreases and oxygen affinity of hemoglobin increases (P50 decreases) with blood storage, leading some to propose that erythrocytes stored for 14 or more days do not release sufficient oxygen to make their transfusion efficacious. The authors tested the hypothesis that erythrocytes stored for 3 weeks are as effective in supplying oxygen to human tissues as are erythrocytes stored for less than 5 h. Methods:Nine healthy volunteers donated 2 units of blood more than 3 weeks before they were tested with a standard, computerized neuropsychological test (digit–symbol substitution test [DSST]) on 2 days, 1 week apart, before and after acute isovolemic reduction of their hemoglobin concentration to 7.4 and 5.5 g/dl. Volunteers randomly received autologous erythrocytes stored for either less than 5 h (“fresh”) or 3 weeks (“stored”) to return their hemoglobin concentration to 7.5 g/dl (double blinded). Erythrocytes of the alternate storage duration were transfused on the second experimental day. The DSST was repeated after transfusion. Results:Acute anemia slowed DSST performance equivalently in both groups. Transfusion of stored erythrocytes with decreased P50 reversed the altered DSST (P < 0.001) to a time that did not differ from that at 7.4 g/dl hemoglobin during production of acute anemia (P = 0.88). The erythrocyte transfusion–induced DSST improvement did not differ between groups (P = 0.96). Conclusion:Erythrocytes stored for 3 weeks are as efficacious as are erythrocytes stored for 3.5 h in reversing the neurocognitive deficit of acute anemia. Requiring fresh rather than stored erythrocytes for augmentation of oxygen delivery does not seem warranted.