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Biomedical subjects

Eugene W Moretti

Publications and source records attributed to Eugene W Moretti.

8 recordsLinked to original sources

Effects of decreased preoperative endotoxin core antibody levels on long-term mortality after coronary artery bypass graft surgery.

HYPOTHESIS: Decreased preoperative levels of antiendotoxin core antibody (EndoCAb) in patients undergoing cardiac surgery with cardiopulmonary bypass are associated with increased long-term mortality. DESIGN: Observational study. SETTING: Academic medical center. PATIENTS: A total of 474 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. INTERVENTIONS: Preoperative serum IgM EndoCAb levels were determined, and established preoperative risk factors were assessed. Patients were assigned a risk score using a validated method. MAIN OUTCOME MEASURES: The primary end point was mortality. Statistical analysis used the Cox proportional hazards regression model with log EndoCAb as the predictor of interest and Parsonnet additive risk score as a covariate. Kaplan-Meier survival curves were generated to visually compare groups with high vs low EndoCAb levels. RESULTS: Forty-six deaths occurred in 5 years. Annual follow-up rates during the 5 years were 100%, 94%, 93%, 98%, and 98% for the 1-, 2-, 3-, 4-, and 5-year periods, respectively. Parsonnet additive risk score (hazard ratio, 1.07; 95% confidence interval [CI], 1.04-1.11; P < .001) and log EndoCAb (hazard ratio, 0.73; 95% CI, 0.53-0.99; P = .04) were independent predictors of long-term mortality in the final model. Kaplan-Meier analysis revealed that the preoperative EndoCAb level was significantly associated with mortality up to 5 years (P = .01 by log-rank test). CONCLUSION: Lower preoperative serum EndoCAb level is a significant predictor of long-term mortality independent of other known risk factors.

Biomarkers↗

Changes in hematocrit based on incremental blood sampling: mathematical models perform poorly.

PURPOSE: Excessive blood sampling, with its inherent risks, is of growing concern among clinicians. We performed this study to measure the changes in hematocrit (Hct) during a laboratory investigation where multiple blood samples are collected. The performance of a simple mathematical model, used in clinical practice to predict Hct changes, is evaluated. METHODS: Eight healthy male volunteers participated in this study. The equation Hct(f) = Hct(i)*(EBV-BL)/EBV is used to predict changes in Hct. Where Hct(f) and Hct(i) are, respectively, the final and initial Hct, EBV is the estimated blood volume and BL is the blood loss. RESULTS: Thirty-five pharmacokinetic samples per subject were collected totalling 314 mL of BL. The Hct decreased from 44.2% +/- 2.2% to 39.9% +/- 2.5% (P = 0.001). On average, model predictions tended to have a discrete tendency to underestimate the Hct changes (-0.5% points of bias). While the predictions of the Hct were very accurate in 50% of the subjects, the discrepancy of the Hct predictions was clinically significant in the other 50% of the subjects. CONCLUSION: Consistent with the model prediction, this study demonstrated a significant reduction in the Hct values in healthy subjects undergoing incremental phlebotomy. On average, the model successfully predicted the decrease in Hct. However, the inter- and intra-individual variabilities in the Hct changes are clinically significant. In clinical settings, which are not well controlled environments, the variability is likely to be greater and the clinical use of the model cannot replace the need to monitor the Hct.

Adult↗

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 APOepsilon3 allele (one or two copies) had a lower incidence of severe sepsis than patients with no APOepsilon3 allele (p = .014), with a relative risk of 0.284 (95% confidence interval 0.127-0.635). The protective effect of APOepsilon3 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 APOepsilon3 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 APOepsilon3 allele is associated with decreased incidence of severe sepsis and a shorter ICU length of stay.

APACHE↗

Dexmedetomidine pharmacodynamics: part I: crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers.

BACKGROUND: Dexmedetomidine, a highly selective alpha2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients, has minimal effect on ventilation. METHODS: This study compared the respiratory effect of dexmedetomidine to that of remifentanil. The authors measured and compared respiratory responses of six healthy male volunteers during (1) a stepwise target-controlled infusion of remifentanil, (2) a stepwise target-controlled infusion of dexmedetomidine, and (3) a pseudonatural sleep session. RESULTS: Compared with baseline, remifentanil infusions resulted in respiratory depression as evidenced by a decrease in respiratory rate and minute ventilation, respiratory acidosis, and apnea episodes resulting in desaturations. Remifentanil disturbed the natural pattern of breathing and flattened the distribution of ventilatory timing (inspiratory time/ventilatory cycle time). The respiratory effects of dexmedetomidine markedly contrasted with those of remifentanil. When compared with baseline, during dexmedetomidine infusions, the respiratory rate significantly increased, and the overall apnea/hypopnea index significantly decreased. The distribution of inspiratory time/ventilatory cycle time showed an increased peak. In addition, dexmedetomidine seemed to mimic some aspect of natural sleep. While the subjects were breathing a 5% CO2 mixture, hypercapnic arousal phenomena (documented by the Bispectral Index, the electroencephalogram, and sudden increase in the minute ventilation) were observed during dexmedetomidine infusions. Similar phenomena during natural sleep have been reported in the literature. CONCLUSIONS: In comparison with remifentanil, dexmedetomidine infusions (1) did not result in clinically significant respiratory depression, (2) decreased rather than increased the apnea/hypopnea index, and (3) exhibited some similarity with natural sleep.

Adult↗

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

BACKGROUND: Dexmedetomidine is a highly selective alpha2-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 degrees to 50 degrees 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 degrees C at baseline to 48.4 degrees and 49.1 degrees C during remifentanil infusions) without a change of the steepness of the curve (identical Hill coefficients gamma during baseline and remifentanil). Compared to baseline, dexmedetomidine infusions resulted in both a right shift of the sigmoid curve (increased T50 to 47.2 degrees C) and a decrease in the steepness of the curve (decreased gamma 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 gamma). 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.

Adult↗

The relationship between ionized and total serum magnesium concentrations during abdominal surgery.

STUDY OBJECTIVE: To determine the necessity for ionized magnesium (iMg) assay by evaluating the effect of abdominal surgery without massive transfusion on total magnesium (Mg) and iMg concentrations. DESIGN: Prospective, observational study. SETTING: Operating rooms at a university teaching hospital. PATIENTS: 31 patients without electrolyte abnormalities who were scheduled for abdominal surgery. INTERVENTIONS: None. MEASUREMENTS: Serum electrolytes, iMg, ionized calcium, proteins before and after surgery, and urine Mg were recorded. MAIN RESULTS: Total Mg and iMg decreased: Mg 23%, iMg 15%; p < 0.0001. Total and iMg were highly correlated (r = 0.728, p < 0.0001). Urine Mg output remained within normal limits (mean 0.24 mmol/hr). CONCLUSIONS: During abdominal surgery without massive transfusion, both total and ionized hypomagnesemia occur. Changes in iMg and total serum Mg concentrations are closely correlated. Total serum Mg assay, while overestimating the prevalence of ionized hypomagnesemia, is sufficient to screen for hypomagnesemia.

Abdomen↗

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.

Antiemetics↗

Orthotopic liver transplant patients require less postoperative morphine than do patients undergoing hepatic resection.

STUDY OBJECTIVE: To compare postoperative morphine use, analgesic efficacy, and side effect profiles in patients following orthotopic liver transplantation (OLTx) and liver resection (LR). DESIGN: Retrospective study. SETTING: Liver transplant and liver resection surgery at a university hospital. PATIENTS: 25 ASA physical status I, II, III, and IV patients undergoing OLTx or liver resection. MEASUREMENTS AND MAIN RESULTS: Morphine use was significantly decreased in the OLTx patients at 6,12, 24, 48, and 72 hours following commencement of patient-controlled analgesia. After commencement of patient-controlled analgesia, pain scores were significantly reduced in the OLTx group compared with those in the liver resection group at 6 and 12 hours. CONCLUSIONS: Orthotopic liver transplant patients experienced less pain and used less morphine postoperatively than did liver resection patients.

Adult↗