Eugene W. Moretti

Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery.

Background Intraoperative hypovolemia is common and is a potential cause of organ dysfunction, increased postoperative morbidity, length of hospital stay, and death. The objective of this prospective, randomized study was to assess the effect of goal-directed intraoperative fluid administration on length of postoperative hospital stay. Methods One hundred patients who were to undergo major elective surgery with an anticipated blood loss greater than 500 ml were randomly assigned to a control group (n = 50) that received standard intraoperative care or to a protocol group (n = 50) that, in addition, received intraoperative plasma volume expansion guided by the esophageal Doppler monitor to maintain maximal stroke volume. Length of postoperative hospital stay and postoperative surgical morbidity were assessed. Results Groups were similar with respect to demographics, surgical procedures, and baseline hemodynamic variables. The protocol group had a significantly higher stroke volume and cardiac output at the end of surgery compared with the control group. Patients in the protocol group had a shorter duration of hospital stay compared with the control group: 5 ± 3 versus 7 ± 3 days (mean ± SD), with a median of 6 versus 7 days, respectively (P = 0.03). These patients also tolerated oral intake of solid food earlier than the control group: 3 ± 0.5 versus 4.7 ± 0.5 days (mean ± SD), with a median of 3 versus 5 days, respectively (P = 0.01). Conclusions Goal-directed intraoperative fluid administration results in earlier return to bowel function, lower incidence of postoperative nausea and vomiting, and decrease in length of postoperative hospital stay.

Dexmedetomidine pharmacodynamics: Part II: Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers.

Background:Dexmedetomidine is a highly selective &agr;2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients. The analgesic profile of dexmedetomidine has not been fully characterized in humans. Methods:This study was designed to compare the analgesic responses of six healthy male volunteers during stepwise target-controlled infusions of remifentanil and dexmedetomidine. A computer-controlled thermode was used to deliver painful heat stimuli to the volar side of the forearms of the subjects. Six sequential 5-s stimuli (ranging from 41° to 50°C) were delivered in random order. The recorded visual analog scale was used to fit an Emax model. Results:Compared to baseline, remifentanil infusions resulted in a right shift of the sigmoid curve (increased T50, the temperature producing a visual analog scale score of 50% of the maximal effect, from 46.1°C at baseline to 48.4° and 49.1°C during remifentanil infusions) without a change of the steepness of the curve (identical Hill coefficients &ggr; during baseline and remifentanil). Compared to baseline, dexmedetomidine infusions resulted in both a right shift of the sigmoid curve (increased T50 to 47.2°C) and a decrease in the steepness of the curve (decreased &ggr; from 3.24 during baseline and remifentanil infusions to 2.45 during dexmedetomidine infusions). There was no difference in the pain responses between baseline and after recovery from remifentanil infusions (identical T50 and &ggr;). Conclusion:As expected, dexmedetomidine is not as effective an analgesic as the opioid remifentanil. The difference in the quality of the analgesia with remifentanil may be a reflection of a different mechanism of action or a consequence of the sedative effect of dexmedetomidine.

A prospective, multicenter derivation of a biomarker panel to assess risk of organ dysfunction, shock, and death in emergency department patients with suspected sepsis

Objective:To define a biomarker panel to predict organ dysfunction, shock, and in-hospital mortality in emergency department (ED) patients with suspected sepsis. Design:Prospective observational study. Setting:EDs of ten academic medical centers. Patients:There were 971 patients enrolled. Inclusion criteria: 1) ED patients age > 18; 2) suspected infection or a serum lactate level > 2.5 mmol/L; and 3) two or more systemic inflammatory response syndrome criteria. Exclusion criteria: pregnancy, do-not-resuscitate status, or cardiac arrest. Measurements and Main Results:Nine biomarkers were assayed from blood draws obtained on ED presentation. Multivariable logistic regression was used to identify an optimal combination of biomarkers to create a panel. The derived formula for weighting biomarker values was used to calculate a “sepsis score,” which was the predicted probability of the primary outcome of severe sepsis (sepsis plus organ dysfunction) within 72 hrs. We also assessed the ability of the sepsis score to predict secondary outcome measures of septic shock within 72 hrs and in-hospital mortality. The overall rates of each outcome were severe sepsis, 52%; septic shock, 39%; and in-hospital mortality 7%. Among the nine biomarkers tested, the optimal 3-marker panel was neutrophil gelatinase-associated lipocalin, protein C, and interleukin−1 receptor antagonist. The area under the curve for the accuracy of the sepsis score derived from these three biomarkers was 0.80 for severe sepsis, 0.77 for septic shock, and 0.79 for death. When included in multivariate models with clinical variables, the sepsis score remained highly significant (p < 0.001) for all the three outcomes. Conclusions:A biomarker panel of neutrophil gelatinase-associated lipocalin, interleukin-1ra, and Protein C was predictive of severe sepsis, septic shock, and death in ED patients with suspected sepsis. Further study is warranted to prospectively validate the clinical utility of these biomarkers and the sepsis score in risk-stratifying patients with suspected sepsis.

Malnutrition in liver transplant patients: preoperative subjective global assessment is predictive of outcome after liver transplantation.

Background. Malnutrition is a common complication of end-stage liver disease. It is frequently not a priority of treatment before liver transplantation. The purpose of this study was to examine whether prospective preoperative nutritional assessment could predict resource utilization and outcome after liver transplantation. Methods. We retrospectively reviewed 109 sequential orthotopic liver transplants performed at our center between July 1996 and May 1999. Ten patients with fulminant hepatic failure were excluded from the study, leaving 99 patients. Nutritional status was determined at the time of transplantation using subjective global assessment. Wilcoxon rank sum test and rank analysis of variance were used to analyze the data. Results are reported as median (interquartile range). A P value <0.05 was considered significant. Results. Intraoperative transfusion requirements of packed red blood cells and cryoprecipitate was higher in the patients with severe malnutrition in comparison to the mild and moderate groups (severe vs. moderate, 5.5±5.5 vs. 3.0±6, P =0.026; vs. mild, 1.5±3, P <0.0001). The severe group required more fresh-frozen plasma intraoperatively than the mild group (mild vs. severe, 0±2 vs. 2±6, P =0.0007; vs. moderate, 1±4, P =0.071). Patients in the severe group had longer postoperative lengths of stay compared with patients in the moderate and mild groups (severe vs. moderate, 16±9 days vs. 10±5 days, P =0.0027; vs. mild, 9±8 days, P =0.0006). Conclusions. Subjective global assessment is an excellent independent predictor of outcome in patients undergoing liver transplantation. Severely malnourished patients require more blood products during surgery and have prolonged postoperative length of stay in hospital. Our data suggest that if nutritional repletion is possible in patients with end-stage liver disease before transplantation, patient outcomes could be improved.

Minimally Invasive Cardiac Output Monitoring in the Perioperative Setting

With advancing age and increased co-morbidities in patients, the need for monitoring devices during the perioperative period that allow clinicians to track physiologic variables, such as cardiac output (CO), fluid responsiveness and tissue perfusion, is increasing. Until recently, the only tool available to anesthesiologists to monitor CO was either a pulmonary artery catheter or transesophageal echocardiograph. These devices have their limitations and potential for morbidity. Several new devices (including esophageal Doppler monitors, pulse contour analysis, indicator dilution, thoracic bioimpedance and partial non-rebreathing systems) have recently been marketed which have the ability to monitor CO noninvasively and, in some cases, assess the patient’s ability to respond to fluid challenges. In this review, we will describe these new devices including the technology, studies on their efficacy and the limitations of their use.

Intraoperative colloid administration reduces postoperative nausea and vomiting and improves postoperative outcomes compared with crystalloid administration.

The debate over colloid versus crystalloid as the best solution for intraoperative fluid resuscitation is not resolved. Published studies have shown that mortality is not related to the specific fluid used for resuscitation. In addition, the quality of postoperative recovery between colloid and crystalloid has not been well investigated. In a prospective, blinded fashion, we investigated the effects of colloid and crystalloid resuscitation on nausea and vomiting and on the postoperative patient recovery profile. Patients undergoing major elective noncardiac surgery were randomized to receive 6% hetastarch in saline (HS-NS), 6% hetastarch in balanced salt (HS-BS), or lactated Ringer’s solution (LR) on the basis of a fluid administration algorithm. The anesthetic was standardized. Hemodynamic targets included maintenance of arterial blood pressure, heart rate, and urine output within a predefined range. A postoperative morbidity survey was performed at baseline and daily after surgery. Ninety patients participated in the study, with 30 patients in each group. The amounts of study fluid (mean ± sd) administered were 1301 ± 1079 mL, 1448 ± 759 mL, and 5946 ± 1909 mL for the HS-NS, HS-BS, and LR groups, respectively (P < 0.05, HS-NS and HS-BS versus LR). Both the HS-NS and HS-BS (colloid) groups had a significantly less frequent incidence of nausea and vomiting, use of rescue antiemetics, severe pain, periorbital edema, and double vision. We concluded that intraoperative fluid resuscitation with colloid, when compared with crystalloid administration, is associated with an improvement in the quality of postoperative recovery.

The Diagnostic Accuracy of Plasma Neutrophil Gelatinase–Associated Lipocalin in the Prediction of Acute Kidney Injury in Emergency Department Patients With Suspected Sepsis

STUDY OBJECTIVE We assess the diagnostic accuracy of plasma neutrophil gelatinase-associated lipocalin (NGAL) to predict acute kidney injury in emergency department (ED) patients with suspected sepsis. METHODS We conducted a secondary analysis of a prospective observational study of a convenience sample of patients from 10 academic medical center EDs. Inclusion criteria were adult patients aged 18 years or older, with suspected infection or a serum lactate level greater than 2.5 mmol/L; 2 or more systemic inflammatory response syndrome criteria; and a subsequent serum creatinine level obtained within 12 to 72 hours of enrollment. Exclusion criteria were pregnancy, do-not-resuscitate status, cardiac arrest, or dialysis dependency. NGAL was measured in plasma collected at ED presentation. Acute kidney injury was defined as an increase in serum creatinine measurement of greater than 0.5 mg/dL during 72 hours. RESULTS There were 661 patient enrolled, with 24 cases (3.6%) of acute kidney injury that developed within 72 hours after ED presentation. Median plasma NGAL levels were 134 ng/mL (interquartile range 57 to 277 ng/mL) in patients without acute kidney injury and 456 ng/mL (interquartile range 296 to 727 ng/mL) in patients with acute kidney injury. Plasma NGAL concentrations of greater than 150 ng/mL were 96% sensitive (95% confidence interval [CI] 79% to 100%) and 51% (95% CI 47% to 55%) specific for acute kidney injury. In comparison, to achieve equivalent sensitivity with initial serum creatinine level at ED presentation required a cutoff of 0.7 mg/dL and resulted in specificity of 17% (95% CI 14% to 20%). CONCLUSION In this preliminary investigation, increased plasma NGAL concentrations measured on presentation to the ED in patients with suspected sepsis were associated with the development of acute kidney injury. Our findings support NGAL as a promising new biomarker for acute kidney injury; however, further research is warranted.

The desaturation response time of finger pulse oximeters during mild hypothermia

Pulse oximeters may delay displaying the correct oxygen saturation during the onset of hypoxia. We investigated the desaturation response times of pulse oximeter sensors (forehead, ear and finger) during vasoconstriction due to mild hypothermia and vasodilation caused by glyceryl trinitrate. Ten healthy male volunteers were given three hypoxic challenges of 3 min duration under differing experimental conditions. Mild hypothermia increased the mean response time of finger oximeters from 130 to 215 s. Glyceryl trinitrate partly offset this effect by reducing the response time from 215 to 187 s. In contrast, the response times of the forehead and ear oximeters were unaffected by mild hypothermia, but the difference between head and finger oximeters was highly significant (p < 0.0001). The results suggest that the head oximeters provide a better monitoring site for pulse oximeters during mild hypothermia.

APOE polymorphism is associated with risk of severe sepsis in surgical patients

Objective:To test for an association between apolipoprotein E (APOE) genotypes and the occurrence of severe sepsis in an elective surgical cohort. Design:Prospective, observational, single cohort study. Setting:Sixteen-bed surgical intensive care unit (ICU) at a university hospital. Patients:Patients were 343 patients with planned admission to the ICU after major elective noncardiac surgery. Interventions:Blood samples, together with demographic data, baseline clinical data, and Acute Physiology and Chronic Health Evaluation II scores, were collected on admission to the ICU and on each subsequent ICU day. APOE genotyping was conducted using a polymerase chain reaction-based assay. The primary outcome was diagnosis of severe sepsis; secondary outcomes included time on mechanical ventilation, ICU length of stay, and ICU mortality. Measurements and Main Results:Severe sepsis was diagnosed in 34 of 343 patients (9.9%). Carriers of the APO&egr;3 allele (one or two copies) had a lower incidence of severe sepsis than patients with no APO&egr;3 allele (p = .014), with a relative risk of 0.284 (95% confidence interval 0.127–0.635). The protective effect of APO&egr;3 genotype on the incidence of severe sepsis remained significant (p < .01) after adjusting for age, gender, or race in a logistic regression model. Supporting our findings, presence of the APO&egr;3 allele was also associated with fewer days spent in the ICU (p = .007). In contrast, APOE genotypes were not associated with duration of mechanical ventilation or ICU mortality. Conclusions:In an elective surgical cohort, presence of the APO&egr;3 allele is associated with decreased incidence of severe sepsis and a shorter ICU length of stay.

The Accuracy of a Near-Infrared Spectroscopy Cerebral Oximetry Device and Its Potential Value for Estimating Jugular Venous Oxygen Saturation

BACKGROUND:An intriguing potential clinical use of cerebral oximeter measurements (SctO2) is the ability to noninvasively estimate jugular bulb venous oxygen saturation (SjvO2). Our purpose in this study was to determine the accuracy of the FORE-SIGHT® (CAS Medical Systems, Branford, CT), which is calibrated to a weighted average of 70% (SjvO2) and 30% arterial saturation, for Food and Drug Administration pre-market approval 510(k) certification by adapting an industry standard protocol, ISO 9919:2005 (www.ISO.org) (used for pulse oximeters), and to evaluate the use of SctO2 and SpO2 measurements to noninvasively estimate jugular venous oxygen saturation (SnvO2). METHODS:Paired blood gas samples from the radial artery and the jugular venous bulb were collected from 20 healthy volunteers undergoing progressive oxygen desaturation from 100% to 70%. The blood sample pairs were analyzed via co-oximetry and used to calculate the approximate mixed vascular cerebral blood oxygen saturation, or reference SctO2 values (refSctO2), during increasing hypoxia. These reference values were compared to bilateral FORE-SIGHT SctO2 values recorded simultaneously with the blood gas draws to determine its accuracy. Bilateral SctO2 and SpO2 measurements were then used to calculate SnvO2 values which were compared to SjvO2. RESULTS:Two hundred forty-six arterial and 253 venous samples from 18 subjects were used in the analysis. The ipsilateral FORE-SIGHT SctO2 values showed a tolerance interval (TI) of [−10.72 to 10.90] and Lin concordance correlation coefficient (CCC) with standard error (SE) of 0.83 ± 0.073 with the refSctO2 values calculated using arterial and venous blood gases. The ipsilateral data had a CCC of 0.81 + 0.059 with TI of [−9.22 to 9.40] with overall bias of 0.09%, and amplitude of the root mean square of error after it was corrected with random effects analysis was 2.92%. The bias and variability values between the ipsilateral and the contralateral FORE-SIGHT SctO2 measurements varied from person to person. The SnvO2 calculated from the ipsilateral SctO2 and SpO2 data showed a CCC ± SE of 0.79 ± 0.088, TI = [−14.93 to 15.33], slope of 0.98, y-intercept of 1.14% with SjvO2 values with a bias of 0.20% and an Arms of 4.08%. The SnvO2 values calculated independently from contralateral forehead FORE-SIGHT SctO2 values were not as correlated with the SjvO2 values (contralateral side CCC + SE = 0.72 ± 0.118, TI = [−14.86 to 15.20], slope of 0.66, and y-intercept of 20.36%). CONCLUSIONS:The FORE-SIGHT cerebral oximeter was able to estimate oxygen saturation within the tissues of the frontal lobe under conditions of normocapnia and varying degrees of hypoxia (with 95% confidence interval of [−5.60 to 5.78] with ipsilateral blood sample data). These findings from healthy volunteers also suggest that the use of the calculated SnvO2 derived from SctO2 and SpO2 values may be a reasonable noninvasive method of estimating SjvO2 and therefore global cerebral oxygen consumption in the clinical setting. Further laboratory and clinical research is required to define the clinical utility of near-infrared spectroscopy determination of SctO2 and SnvO2 in the operating room setting.