Laurie Doolan

Prospective controlled trial of effect of medical emergency team on postoperative morbidity and mortality rates

ObjectiveTo determine whether the introduction of an intensive care unit-based medical emergency team, responding to hospital-wide preset criteria of physiologic instability, would decrease the rate of predefined adverse outcomes in patients having major surgery. DesignProspective, controlled before-and-after trial. SettingUniversity-affiliated hospital. PatientsConsecutive patients admitted to hospital for major surgery during a 4-month control phase and during a 4-month intervention phase. InterventionsIntroduction of a hospital-wide intensive care unit-based medical emergency team to evaluate and treat in-patients deemed at risk of developing an adverse outcome by nursing, paramedical, and/or medical staff. Measurements and Main ResultsWe measured incidence of serious adverse events, mortality after major surgery, and mean duration of hospital stay. There were 1,369 operations in 1,116 patients during the control period and 1,313 in 1,067 patients during the medical emergency team intervention period. In the control period, there were 336 adverse outcomes in 190 patients (301 outcomes/1,000 surgical admissions), which decreased to 136 in 105 patients (127 outcomes/1,000 surgical admissions) during the intervention period (relative risk reduction, 57.8%; p < .0001). These changes were due to significant decreases in the number of cases of respiratory failure (relative risk reduction, 79.1%; p < .0001), stroke (relative risk reduction, 78.2%; p = .0026), severe sepsis (relative risk reduction, 74.3%; p = .0044), and acute renal failure requiring renal replacement therapy (relative risk reduction, 88.5%; p < .0001). Emergency intensive care unit admissions were also reduced (relative risk reduction, 44.4%; p = .001). The introduction of the medical emergency team was also associated with a significant decrease in the number of postoperative deaths (relative risk reduction, 36.6%; p = .0178). Duration of hospital stay after major surgery decreased from a mean of 23.8 days to 19.8 days (p = .0092). ConclusionsThe introduction of an intensive care unit-based medical emergency team in a teaching hospital was associated with a reduced incidence of postoperative adverse outcomes, postoperative mortality rate, and mean duration of hospital stay.

Sodium bicarbonate to prevent increases in serum creatinine after cardiac surgery: a pilot double-blind, randomized controlled trial

Objective:To test whether perioperative sodium bicarbonate infusion can attenuate postoperative increases in serum creatinine in cardiac surgical patients. Design:Double-blind, randomized controlled trial. Setting:Operating rooms and intensive care unit at a tertiary hospital. Patients:Cohort of 100 cardiac surgical patients at increased risk of postoperative acute renal dysfunction. Intervention:Patients were randomized to either 24 hrs of intravenous infusion of sodium bicarbonate (4 mmol/kg) or sodium chloride (4 mmol/kg). Measurements and Main Results:The primary outcome measure was the proportion of patients developing acute renal dysfunction defined as a postoperative increase in plasma creatinine concentration >25% of baseline within the first five postoperative days. Secondary outcomes included changes in plasma creatinine, plasma urea, urinary neutrophil gelatinase-associated lipocalin, and urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio. Patients were well balanced for baseline characteristics. Sodium bicarbonate infusion increased plasma bicarbonate concentration (p < 0.001), base excess (p < 0.001), plasma pH (p < 0.001), and urine pH (p < 0.001). Fewer patients in the sodium bicarbonate group (16 of 50) developed a postoperative increase in serum creatinine compared with control (26 of 50) (odds ratio 0.43 [95% confidence interval 0.19–0.98]), (p = 0.043). The increase in plasma creatinine, plasma urea, urinary neutrophil gelatinase-associated lipocalin, and urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio was less in patients receiving sodium bicarbonate, (p = 0.014; p = 0.047; p = 0.009; p = 0.004). There were no significant side effects. Conclusions:Sodium bicarbonate loading and continuous infusion was associated with a lower incidence of acute renal dysfunction in cardiac surgical patients undergoing cardiopulmonary bypass. The findings of this pilot study justify further investigation. (ClinicalTrials.gov, NCT00334191).

Phase II, randomized, controlled trial of high-dose N-acetylcysteine in high-risk cardiac surgery patients

Objective:To assess the effect of high-dose N-acetylcysteine on renal function in cardiac surgery patients at higher risk of postoperative renal failure. Design:Multiblind, placebo-controlled, randomized, phase II clinical trial. Setting:Operating rooms and intensive care units of two tertiary referral hospitals. Patients:A total of 60 cardiac surgery patients at higher risk of postoperative renal failure. Interventions:Patients were allocated to either 24 hrs of high-dose N-acetylcysteine infusion (300 mg/kg body weight in 5% glucose, 1.7 L) or placebo (5% glucose, 1.7 L). Measurements and Main Results:The primary outcome measure was the absolute change in serum creatinine from baseline to peak value within the first five postoperative days. Secondary outcomes included the relative change in serum creatinine, peak serum creatinine level, serum cystatin C, and in urinary output. Further outcomes were needed for renal replacement therapy, length of ventilation, and length of stay in the intensive care unit and hospital. Randomization was successful and patients were well balanced for preoperative and intraoperative characteristics. There was no significant attenuation in the increase in serum creatinine from baseline to peak when comparing N-acetylcysteine with placebo (64.5 ± 91.2 and 38.0 ± 42.4 &mgr;mol/L, respectively; p = .15). Also, there was no attenuation in the increase in serum cystatin C from baseline to peak for N-acetylcysteine compared with placebo (0.45 ± 0.43 and 0.30 ± 0.33 mg/L, respectively; p = .40). Likewise, there was no evidence for differences in any other clinical outcome. Conclusions:In this phase II, randomized, controlled trial, high-dose N-acetylcysteine was no more effective than placebo in attenuating cardiopulmonary bypass–related acute renal failure in high-risk cardiac surgery patients.

Early and intensive continuous hemofiltration for severe renal failure after cardiac surgery

BACKGROUND The aim of this study was to test whether early and intensive use of continuous venovenous hemofiltration (CVVH) achieved a better than predicted outcome in patients with severe acute renal failure undergoing cardiac operations, and whether a simple and yet accurate model could be developed to predict their outcome before starting CVVH. METHODS Medical record analysis with collection of demographic, clinical, and outcome information was used. RESULTS Sixty-five consecutive patients were treated with early and intensive CVVH (mean operation to CVVH time, 2.38 days; pump-controlled ultrafiltration rate, 2 L/h) after coronary artery bypass grafting (56.9%), single valve procedure (16.9%), or combined operations (26.2%). In 32.3% of patients, intraaortic balloon counterpulsation was required and 20% of patients were emergencies. Sustained hypotension despite inotropic and vasopressor support occurred in 40% of patients and prolonged mechanical ventilation in 58.5%. Using an outcome prediction score specific for acute renal failure, the predicted risk of death was 66%. Actual mortality was 40% (p = 0.003). Using multivariate logistic regression analysis and neural network analysis, patient outcome could be predicted with good levels of accuracy (receiver operating characteristic 0.89 and 0.9, respectively). CONCLUSIONS Early and aggressive CVVH is associated with better than predicted survival in severe acute renal failure after cardiac operations. Using readily available clinical data, the outcome of such patients can be predicted before the implementation of CVVH.

Bench-to-bedside review: Inotropic drug therapy after adult cardiac surgery – a systematic literature review

Many adult patients require temporary inotropic support after cardiac surgery. We reviewed the literature systematically to establish, present and classify the evidence regarding choice of inotropic drugs. The available evidence, while limited in quality and scope, supports the following observations; although all β-agonists can increase cardiac output, the best studied β-agonist and the one with the most favourable side-effect profile appears to be dobutamine. Dobutamine and phosphodiesterase inhibitors (PDIs) are efficacious inotropic drugs for management of the low cardiac output syndrome. Dobutamine is associated with a greater incidence of tachycardia and tachyarrhythmias, whereas PDIs often require the administration of vasoconstrictors. Other catecholamines have no clear advantages over dobutamine. PDIs increase the likelihood of successful weaning from cardiopulmonary bypass as compared with placebo. There is insufficient evidence that inotropic drugs should be selected for their effects on regional perfusion. PDIs also increase flow through arterial grafts, reduce mean pulmonary artery pressure and improve right heart performance in pulmonary hypertension. Insufficient data exist to allow selection of a specific inotropic agent in preference over another in adult cardiac surgery patients. Multicentre randomized controlled trials focusing on clinical rather than physiological outcomes are needed.

An extracorporeal membrane oxygenation-based approach to cardiogenic shock in an older population.

BACKGROUND We investigated the efficacy of an integrated system of advanced supportive care based on extracorporeal membrane oxygenation (ECMO) in older patients with an estimated mortality of more than 90% to establish whether its use is justifiable. METHODS Treatment was provided by cardiac surgeons and critical care physicians and included the following key elements: (1) ECMO, (2) early application of continuous venovenous hemofiltration, (3) inhaled nitric oxide, (4) maintenance of perfusion pressure with norepinephrine, (5) maintenance of pulmonary blood flow by ventricular filling with intravenous colloids, (6) avoidance of early postoperative anticoagulation, (7) frequent use of transesophageal echocardiography, and (8) low tidal volume ventilation. Demographic features, intraoperative details, postoperative course, ECMO weaning rate, morbidity, survival to hospital discharge, and the quality of life of survivors were recorded. RESULTS Seventeen consecutive patients (median age, 69 years) with refractory cardiogenic shock were studied. The median duration of ECMO was 86 hours (20 to 201 hours). Eleven patients (65%) were successfully weaned from ECMO. Seven patients (41%) survived to discharge. The major causes of morbidity were bleeding and leg ischemia. All patients who survived to discharge were alive and well at follow-up (median, 21 months) and reported a satisfactory quality of life. CONCLUSIONS An ECMO-based approach can be used with acceptable results in the treatment of refractory cardiogenic shock, even in older patients.

Direct vasodilator effect of milrinone, an inotropic drug, on arterial coronary bypass grafts

Milrinone is an inotropic drug with vasodilator activity that has been shown to be useful in increasing cardiac output and decreasing wedge pressure. Despite these advantages, it is unknown whether this drug can be used for the treatment of perioperative spasm of coronary bypass grafts. This study was undertaken to investigate the in vitro vascular effect of milrinone on internal thoracic arteries obtained from patients undergoing coronary artery bypass grafting. The results showed that milrinone produced a potent, concentration-dependent, preventive effect on the norepinephrine-induced contraction of internal thoracic arteries, as well as reversing contraction of internal thoracic arteries by receptor-dependent agents, including the thromboxane A2 mimetic U46619, the vasoconstrictor peptide endothelin-1, and the alpha1-adrenal receptor agonist phenylephrine. The relaxing effect of milrinone was weaker, however, on internal thoracic arteries contracted with 25 mmol/L potassium chloride. Comparison of milrinone with other vasodilators, including papaverine, nitroprusside, and glyceryl trinitrate, showed milrinone to be more potent than papaverine but less potent than nitroprusside and glyceryl trinitrate. The inhibitory effect of milrinone on internal thoracic artery contraction appeared as a reduction in contractile force, not as an increase in the values of concentrations of the agonists causing 50% maximal contraction, which indicates that milrinone exerts its vasodilator effect directly on the smooth muscles, not on the membrane receptors. The results also showed no significant difference in relaxing effect between internal thoracic artery rings with and without endothelium. In conclusion, this study provides experimental evidence that milrinone is a potent, endothelium-independent, direct vasodilator of the human internal thoracic artery and provides the scientific rationale for a future clinical trial with this drug for the perioperative treatment of internal thoracic artery spasm in cardiac surgical patients.

Markers of splanchnic perfusion and intestinal translocation of endotoxins during cardiopulmonary bypass: effects of dopamine and milrinone.

OBJECTIVES To investigate markers of splanchnic perfusion and the extent of endotoxemia during cardiopulmonary bypass (CPB) and to compare the effects of dopamine and milrinone on both splanchnic perfusion and endotoxemia. DESIGN Prospective, randomized, blinded study. SETTING University teaching hospital. PARTICIPANTS Twenty-four patients scheduled for elective coronary artery bypass graft surgery (CABG). INTERVENTIONS Patients were allocated to receive placebo (eight patients), dopamine (eight patients), or milrinone (eight patients) during CPB, and at seven times intraoperatively assays were performed of arterial and hepatic venous endotoxin levels, as well as measurements and/or calculations of intramucosal gastric pH (pHi), arterial and hepatic venous lactate-pyruvate ratio (lac/pyr), and hepatic venous oxygen saturation (S(HV)O2). MEASUREMENTS AND MAIN RESULTS Both splanchnic and systemic endotoxin levels increased significantly, and this was unaffected by either dopamine or milrinone. Gastric pHi did not change, and there were only modest increases in lac/pyr, which remained within the normal range of less than 10 in both splanchnic and systemic blood. In the placebo group, S(HV)O2 decreased at the onset of CPB and also significantly decreased during rewarming and at the end of CPB and surgery. In the dopamine-treated patients, S(HV)O2 was greater compared with placebo and milrinone during both hypothermic and rewarming phases. CONCLUSION Endotoxemia occurs during routine CPB. Neither pHi nor lac/pyr values showed adverse change, but hepatic venous oximetry may be a more sensitive indicator of splanchnic dysoxia in that S(HV)O2 was reduced during rewarming. Whether dopamine or milrinone confer protection against splanchnic ischemia remains uncertain.

On-pump coronary artery surgery versus off-pump exclusive arterial coronary grafting: a matched cohort comparison

BACKGROUND It is unknown whether coronary artery bypass grafting without cardiopulmonary bypass and with exclusive use of arterial grafts (arterial off-pump CABG) offers any significant short-term advantages over standard CABG with cardiopulmonary bypass. Accordingly, we performed a comparison of the short-term outcomes of arterial off-pump and standard CABG patients matched for preoperative risk and number of grafts. METHODS We studied 90 consecutive arterial off-pump CABG patients during a 2-year period, obtained demographic and clinical features and surgical characteristics, and calculated their predicted surgical risk (EuroSCORE). Using a database of 750 contemporaneous patients treated with standard CABG, we created a matched cohort of 90 patients using an iterative process prioritizing number of grafts, target vessels, EuroSCORE, age, and sex. We compared the two groups for baseline features and short-term clinical outcomes. RESULTS There were no differences in age (65.9 versus 64.7 years), sex, EuroSCORE (3.3 versus 3. 6), number of grafts (2.1 versus 2.1), and preoperative left ventricular function. Arterial off-pump CABG, however, was associated with decreased duration of operation (213 versus 252 minutes; p < 0.0013), decreased peak postoperative troponin I levels (mean, 10.8 versus 29.1 ng/mL; p < 0.0001), decreased peak norepinephrine dose (2.3 versus 4.1 microg/ min; p < 0.0082), and decreased likelihood of receiving red blood cell transfusion (17.8% versus 40%; p = 0.0016). There were no differences in duration of intensive care unit or hospital stay, incidence of atrial fibrillation, or other clinical complications. There was one death in each group. CONCLUSIONS After matching for number of grafts and other important preoperative risk markers, arterial off-pump CABG still decreases the need for red blood cell transfusion and offers other moderate clinical advantages compared with standard on-pump CABG.

EFFECT OF HOMOCYSTEINE AND CHOLESTEROL IN RAISING PLASMA HOMOCYSTEINE, CHOLESTEROL AND TRIGLYCERIDE LEVELS

A high plasma homocysteine level is a newly regarded risk factor for coronary artery disease. We report a synergistic effect of homocysteine plus cholesterol feeding on further raising total plasma homocysteine, cholesterol and triglycerides levels than each agent alone, which further enhances the risk of coronary artery disease.