Scott D. Kelley

Hospital Stay and Mortality Are Increased in Patients Having a "Triple Low" of Low Blood Pressure, Low Bispectral Index, and Low Minimum Alveolar Concentration of Volatile Anesthesia

Background: Low mean arterial pressure (MAP) and deep hypnosis have been associated with complications and mortality. The normal response to high minimum alveolar concentration (MAC) fraction of anesthetics is hypotension and low Bispectral Index (BIS) scores. Low MAP and/or BIS at lower MAC fractions may represent anesthetic sensitivity. The authors sought to characterize the effect of the triple low state (low MAP and low BIS during a low MAC fraction) on duration of hospitalization and 30-day all-cause mortality. Methods: Mean intraoperative MAP, BIS, and MAC were determined for 24,120 noncardiac surgery patients at the Cleveland Clinic, Cleveland, Ohio. The hazard ratios associated with combinations of MAP, BIS, and MAC values greater or less than a reference value were determined. The authors also evaluated the association between cumulative triple low minutes, and excess length-of-stay and 30-day mortality. Results: Means (±SD) defining the reference, low, and high states were 87 ± 5 mmHg (MAP), 46 ± 4 (BIS), and 0.56 ± 0.11 (MAC). Triple lows were associated with prolonged length of stay (hazard ratio 1.5, 95% CI 1.3–1.7). Thirty-day mortality was doubled in double low combinations and quadrupled in the triple low group. Triple low duration ≥60 min quadrupled 30-day mortality compared with ⩽15 min. Excess length of stay increased progressively from ⩽15 min to ≥60 min of triple low. Conclusions: The occurrence of low MAP during low MAC fraction was a strong and highly significant predictor for mortality. When these occurrences were combined with low BIS, mortality risk was even greater. The values defining the triple low state were well within the range that many anesthesiologists tolerate routinely.

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.

Electrocardiographic ST-segment changes during acute, severe isovolemic hemodilution in humans.

BackgroundControversy exists regarding the lowest blood hemoglobin concentration that can be safely tolerated. The authors studied healthy resting humans to test the hypothesis that acute isovolemic reduction of blood hemoglobin concentration to 5 g/dl would produce an imbalance in myocardial oxygen supply and demand, resulting in myocardial ischemia. MethodsFifty-five conscious healthy human volunteers were studied. Isovolemic removal of aliquots of blood reduced blood hemoglobin concentration from 12.8 ± 1.2 to 5.2 ± 0.5 g/dl (mean ± SD). Removed blood was replaced simultaneously with intravenous fluids to maintain constant isovolemia. Hemodynamics and arterial oxygen content (Cao2) were measured before and after removal of each aliquot of blood. Electrocardiographic (ECG) changes were monitored continuously using a Holter ECG recorder for detection of myocardial ischemia. ResultsDuring hemodilution, transient, reversible ST-segment depression developed in three subjects as seen on the electrocardiogram during hemodilution. These changes occurred at hemoglobin concentrations of 5–7 g/dl while the subjects were asymptomatic. Two of three subjects with ECG changes had significantly higher heart rates than those without ECG changes at the same hemoglobin concentrations. When evaluating the entire study period, the subjects who had ECG ST-segment changes had significantly higher maximum heart rates than those without ECG changes, despite having similar baseline values. ConclusionWith acute reduction of hemoglobin concentration to 5 g/dl, ECG ST-segment changes developed in 3 of 55 healthy conscious adults and were suggestive of, but not conclusive for, myocardial ischemia. The higher heart rates that developed during hemodilution may have contributed to the development of an imbalance between myocardial supply and demand resulting in ECG evidence of myocardial ischemia. However, these ECG changes appear to be benign because they were reversible and not accompanied by symptoms.

Cardiovascular actions of desflurane in normocarbic volunteers.

The cardiovascular actions of three concentrations of desflurane (formerly I-653), a new inhalation anesthetic, were examined in 12 unmedicated normocapnic, normothermic male volunteers. We compared the effects of 0.83, 1.24, and 1.66 MAC desflurane with measurements obtained while the same men were conscious. Desflurane caused a dose-dependent increase in right-heart filling pressure and a decrease in systemic vascular resistance and mean systemic arterial blood pressure. As measured by echocardiography, left ventricular end-diastolic area did not change except for a small increase at 1.66 MAC desflurane, and systolic wall stress was less at all concentrations of desflurane than during the conscious state. Desflurane did not change cardiac index or left ventricular ejection fraction. Heart rate did not change at 0.83 MAC, but progressively increased with deeper desflurane anesthesia. Stroke volume index was less at all concentrations of desflurane than while the men were conscious, but desflurane did not alter the velocity of ventricular circumferential fiber shortening. Mixed venous blood PO2 and oxyhemoglobin saturation were higher during all concentrations of desflurane anesthesia than during the conscious state. No volunteer developed a metabolic acidosis. We conclude that desflurane with controlled ventilation and constant PaCO2 causes cardiovascular depression, as indicated by the increased cardiac filling pressure and decreased stroke volume index and by no change in the velocity of circumferential fiber shortening in the presence of decreased systolic wall stress. However, cardiac output is well maintained, and heart rate does not increase at light levels of anesthesia. The cardiovascular actions of 0.83 and 1.66 MAC desflurane were also reexamined in 6 of the 12 men during the seventh hour of anesthesia. Prolonged desflurane anesthesia resulted in lesser cardiovascular depression than was evidenced during the first 90 min. The measures of cardiac filling (central venous pressure and left ventricular end-diastolic cross-sectional area) did not differ between the early and late periods of anesthesia. Systemic vascular resistance decreased further during the late period, but systolic wall stress did not differ between the two time periods. During the seventh hour of desflurane anesthesia, heart rate and cardiac index were higher at both anesthetic concentrations than during the first 90 min of anesthesia. Left ventricular ejection fraction and velocity of fiber shortening did not change with duration of desflurane anesthesia. Oxygen consumption, oxygen transport, the ratio of the two, mixed venous PO2, and mixed venous oxyhemoglobin saturation (SO2) increased late in the anesthetic in comparison with the first 90 min.

Broadly applicable risk stratification system for predicting duration of hospitalization and mortality

Background:Hospitals are increasingly required to publicly report outcomes, yet performance is best interpreted in the context of population and procedural risk. We sought to develop a risk-adjustment method using administrative claims data to assess both national-level and hospital-specific performance. Methods:A total of 35,179,507 patient stay records from 2001–2006 Medicare Provider Analysis and Review (MEDPAR) files were randomly divided into development and validation sets. Risk stratification indices (RSIs) for length of stay and mortality endpoints were derived from aggregate risk associated with individual diagnostic and procedure codes. Performance of RSIs were tested prospectively on the validation database, as well as a single institution registry of 103,324 adult surgical patients, and compared with the Charlson comorbidity index, which was designed to predict 1-yr mortality. The primary outcome was the C statistic indicating the discriminatory power of alternative risk-adjustment methods for prediction of outcome measures. Results:A single risk-stratification model predicted 30-day and 1-yr postdischarge mortality; separate risk-stratification models predicted length of stay and in-hospital mortality. The RSIs performed well on the national dataset (C statistics for median length of stay and 30-day mortality were 0.86 and 0.84). They performed significantly better than the Charlson comorbidity index on the Cleveland Clinic registry for all outcomes. The C statistics for the RSIs and Charlson comorbidity index were 0.89 versus 0.60 for median length of stay, 0.98 versus 0.65 for in-hospital mortality, 0.85 versus 0.76 for 30-day mortality, and 0.83 versus 0.77 for 1-yr mortality. Addition of demographic information only slightly improved performance of the RSI. Conclusion:RSI is a broadly applicable and robust system for assessing hospital length of stay and mortality for groups of surgical patients based solely on administrative data.

Immediate tracheal extubation after liver transplantation: Experience of two transplant centers

Early tracheal extubation has been safely performed after large operative procedures, questioning the need for routine postoperative ventilation.Because immediate postoperative tracheal extubation of liver transplantation patients has not been previously reported, we performed preliminary studies at two institutions to evaluate potential risk and cost benefit. At the University of Colorado (UC), extubation criteria were derived from the retrospective analysis of patients who were ventilated less than 8 h and experienced an intensive care unit stay less than 48 h in 1994. Preoperative criteria for age, severity of illness, and absence of encephalopathy and coexistent disease were used in a subsequent prospective study in 1995. Donor graft function, blood use, hemodynamic stability, and alveolar-arterial oxygen gradient served as intraoperative criteria. Cost of intensive care services was compared for the 1994 ventilated patients and the 1995 patients whose tracheas were extubated immediately postoperatively. At the second institution, University of California at San Francisco (UCSF), patients were tracheally extubated immediately postoperatively, based on clinical judgment by the anesthesiologist. A retrospective analysis was then completed. Sixteen of 67 patients at UC and 25 of 106 patients at UCSF were tracheally extubated. There were no reintubations at UC, while 2 of 25 patients at UCSF required reintubation. Prior encephalopathy, poor donor liver function, and an increased alveolar-arterial oxygen gradient were present in the patients who suffered perioperative respiratory failure. Seventeen of 25 patients at UCSF did not have all criteria used at UC but did not require reintubation. Wider limits on age and severity of illness did not preclude successful extubation. Cost analysis at UC showed a significant reduction in intensive care unit services and associated cost for extubated patients. We conclude that immediate postoperative tracheal extubation of selected liver transplantation patients is safe and cost effective. (Anesth Analg 1997;84:249-53)

Heart rate increases linearly in response to acute isovolemic anemia

BACKGROUND : The cardiovascular response to acute isovolemic anemia in humans is thought to differ from that of other species. Studies of anesthetized humans have found either no change or a decreased heart rate. A previous study showed that in 32 healthy unmedicated humans, heart rate increased during acute isovolemic anemia. The hypothesis that heart rate in humans increases in response to acute isovolemic anemia and that the increase is affected by gender was tested.

Venovenous bypass during liver transplantation.

n this issue of Anesthesia and Analgesia, Veroli and colleagues (1) explore an important aspect of the I intraoperative management of liver transplantation: the use of venovenous bypass hemodynamic support during the anhepatic period. Liver transplantation is an effective therapy for a variety of acute and chronic liver diseases that result in hepatic failure. Much of the improvement in survival statistics can be attributed to advances in immunosuppressive management, particularly the introduction of cyclosporine and the earlier recognition of rejection episodes. However, despite nearly 30 yr of clinical experience in human liver transplantation, the intraoperative management of this procedure remains challenging for anesthesiologists and surgeons. The magnitude of the surgical procedure (i.e., total hepatectomy, porta hepatis dissection, four major vascular anastomoses, and biliary reconstruction) in patients with severe liver disease (i.e., portal hypertension, coagulopathy, and thrombocytopenia) accounts for much of the difficulty encountered with this procedure. In addition, the critical part of the operation, the anhepatic period, requires the vascular exclusion of the liver to permit anastomosis and subsequent reperfusion of the hepatic allograft. This time period (30-90 min) is marked by significant changes in cardiovascular indices: decreased filling pressure, decreased cardiac output, increased infrahepatic caval pressure, decreased renal perfusion pressure, and moderately decreased systemic arterial pressure. To attenuate some of these hemodynamic responses, venovenous bypass was introduced to facilitate venous return of blood from the lower extremities and portal system to the upper body (2). Additional perioperative benefits attributed to venovenous bypass include decreased bleeding and transfusion requirement, improved postoperative renal function, decompression of the intestinal vascular bed, and earlier return of intestinal function; a better environment in which to train transplant surgeons is also an important benefit (3). Because the potential benefits of venovenous bypass

Recovery of hepatic drug extraction after hypothermic preservation

Background To determine whether liver preservation before transplantation impairs hepatic drug metabolism, hepatic extraction of drugs with different metabolic pathways (fentanyl, morphine, and vecuronium) in isolated rat livers was measured either immediately or after 24 h of hypothermia at 4 degrees Celsius using a standard preservation‐reperfusion sequence. Methods Isolated rat livers were perfused via the portal vein for 30 min to document initial viability. Test livers (n = 5) were perfused with iced Belzer solution, stored for 24 h at 4 degrees Celsius, and flushed with 6% hetastarch. After hypothermic preservation for 24 h, or in control livers (n = 5) immediately after the 30‐min perfusion, livers were perfused single‐pass at a constant flow rate with solutions containing fentanyl, morphine, and vecuronium at 37 degrees Celsius. Perfusate and bile samples were obtained at regular intervals for 64 min, after which liver tissue was harvested for analysis. Drug concentrations were measured using radioimmunoassay and gas chromatography. Metabolic capacity of the liver was estimated from the extraction fraction of each drug at steady‐state. Results After warming to 37 degrees Celsius, preserved livers consumed oxygen and produced bile at rates similar to that of control livers. Hypothermic preservation did not affect extraction of fentanyl and morphine. Vecuronium extraction was initially less in preserved livers, but this difference disappeared as the preserved livers returned to 37 degrees Celsius (< 16 min). Biliary excretion and tissue concentrations of vecuronium were similar in each group. Conclusions Hypothermic preservation does not significantly impair extraction of these drugs in this liver preservation model. If these results apply to human liver transplantation, little danger of drug accumulation exists during the early postoperative period if hepatic function is normal.

Respiratory rate monitoring: characterizing performance for emerging technologies.

December 2014 • Volume 119 • Number 6 Copyright