Yannick Le Manach

Poor Intraoperative Blood Glucose Control Is Associated with a Worsened Hospital Outcome after Cardiac Surgery in Diabetic Patients

Background: Tight perioperative control of blood glucose improves the outcome of diabetic patients undergoing cardiac surgery. Because stress response and cardiopulmonary bypass can induce profound hyperglycemia, intraoperative glycemic control may become difficult. The authors undertook a prospective cohort study to determine whether poor intraoperative glycemic control is associated with increased intrahospital morbidity. Methods: Two hundred consecutive diabetic patients undergoing on-pump heart surgery were enrolled. A standard insulin protocol based on subcutaneous intermediary insulin was given the morning of the surgery. Intravenous insulin therapy was initiated intraoperatively from blood glucose concentrations of 180 mg/dl or greater and titrated according to a predefined protocol. Poor intraoperative glycemic control was defined as four consecutive blood glucose concentrations greater than 200 mg/dl without any decrease in despite insulin therapy. Postoperative blood glucose concentrations were maintained below 140 mg/dl by using aggressive insulin therapy. The main endpoints were severe cardiovascular, respiratory, infectious, neurologic, and renal in-hospital morbidity. Results: Insulin therapy was required intraoperatively in 36% of patients, and poor intraoperative glycemic control was observed in 18% of patients. Poor intraoperative glycemic control was significantly more frequent in patients with severe postoperative morbidity (37% vs. 10%; P < 0.001). The adjusted odds ratio for severe postoperative morbidity among patients with a poor intraoperative glycemic control as compared with patients without was 7.2 (95% confidence interval, 2.7–19.0). Conclusion: Poor intraoperative control of blood glucose concentrations in diabetic patients undergoing cardiac surgery is associated with a worsened hospital outcome after surgery.

Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a "gray zone" approach.

Background:Respiratory arterial pulse pressure variations (PPV) are the best predictors of fluid responsiveness in mechanically ventilated patients during general anesthesia. However, previous studies were performed in a small number of patients and determined a single cutoff point to make clinical discrimination. The authors sought to test the predictive value of PPV in a large, multicenter study and to express it using a gray zone approach. Methods:The authors studied 413 patients during general anesthesia and mechanical ventilation in four centers. PPV, central venous pressure, and cardiac output were recorded before and after volume expansion (VE). Response to VE was defined as more than 15% increase in cardiac output after VE. The following approaches were used to determine the gray zones: resampled and two-graph receiver operator characteristic curves. The impact of changes in the benefit-risk balance of VE on the gray zone was also evaluated. Results:The authors observed 209 responders (51%) and 204 nonresponders (49%) to VE. The area under receiver operating characteristic curve was 0.89 (95% CI: 0.86–0.92) for PPV, compared with 0.57 (95% CI: 0.54–0.59) for central venous pressure (P < 10−5). The gray zone approach identified a range of PPV values (between 9% and 13%) for which fluid responsiveness could not be predicted reliably. These PPV values were seen in 98 (24%) patients. Changes in the cost ratio of VE moderately affected the gray zone limits. Conclusion:Despite a strong predictive value, PPV may be inconclusive (between 9% and 13%) in approximately 25% of patients during general anesthesia.

Statistical evaluation of a biomarker.

A biomarker may provide a diagnosis, assess disease severity or risk, or guide other clinical interventions such as the use of drugs. Although considerable progress has been made in standardizing the methodology and reporting of randomized trials, less has been accomplished concerning the assessment of biomarkers. Biomarker studies are often presented with poor biostatistics and methodologic flaws that precludes them from providing a reliable and reproducible scientific message. A host of issues are discussed that can improve the statistical evaluation and reporting of biomarker studies. Investigators should be aware of these issues when designing their studies, editors and reviewers when analyzing a manuscript, and readers when interpreting results.

Early and Delayed Myocardial Infarction after Abdominal Aortic Surgery

Background: Although postoperative myocardial infarction (PMI) after vascular surgery has been described to be associated with prolonged ischemia, its exact pathophysiology remains unclear. Methods: The authors used intense cardiac troponin I (cTnI) surveillance after abdominal aortic surgery in 1,136 consecutive patients to better evaluate the incidence and timing of PMI (cTnI ≥ 1.5 ng/ml) or myocardial damage (abnormal cTnI < 1.5 ng/ml). Results: Abnormal cTnI concentrations was noted in 163 patients (14%), of which 106 (9%) had myocardial damage and 57 (5%) had PMI. In 34 patients (3%), PMI was preceded by a prolonged (> 24 h) period of increased cTnI (delayed PMI), and in 21 patients (2%), the increase in cTnI lasted less than 24 h (early PMI). The mean times from end of surgery to PMI were 37 ± 22 and 74 ± 39 h in the early PMI and delayed PMI groups, respectively (P < 0.001). The mean time between the first abnormal cTnI and PMI in the delayed PMI group was 54 ± 35 h, during which the cTnI profiles of the myocardial damage and delayed PMI groups were identical. In-hospital mortality rates were 24, 21, 7, and 3% for the early PMI, delayed PMI, myocardial damage, and normal groups, respectively. Conclusions: Intense postoperative cTnI surveillance revealed two types of PMI according to time of appearance and rate of increase in cTnI. The identification of early and delayed PMI may be suggestive of different pathophysiologic mechanisms. Abnormal but low postoperative cTnI is associated with increased mortality and may lead to delayed PMI.

The prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: A systematic review and individual patient data meta-analysis

OBJECTIVES The objective of this study was to determine whether measuring post-operative B-type natriuretic peptides (NPs) (i.e., B-type natriuretic peptide [BNP] and N-terminal fragment of proBNP [NT-proBNP]) enhances risk stratification in adult patients undergoing noncardiac surgery, in whom a pre-operative NP has been measured. BACKGROUND Pre-operative NP concentrations are powerful independent predictors of perioperative cardiovascular complications, but recent studies have reported that elevated post-operative NP concentrations are independently associated with these complications. It is not clear whether there is value in measuring post-operative NP when a pre-operative measurement has been done. METHODS We conducted a systematic review and individual patient data meta-analysis to determine whether the addition of post-operative NP levels enhanced the prediction of the composite of death and nonfatal myocardial infarction at 30 and ≥180 days after surgery. RESULTS Eighteen eligible studies provided individual patient data (n = 2,179). Adding post-operative NP to a risk prediction model containing pre-operative NP improved model fit and risk classification at both 30 days (corrected quasi-likelihood under the independence model criterion: 1,280 to 1,204; net reclassification index: 20%; p < 0.001) and ≥180 days (corrected quasi-likelihood under the independence model criterion: 1,320 to 1,300; net reclassification index: 11%; p = 0.003). Elevated post-operative NP was the strongest independent predictor of the primary outcome at 30 days (odds ratio: 3.7; 95% confidence interval: 2.2 to 6.2; p < 0.001) and ≥180 days (odds ratio: 2.2; 95% confidence interval: 1.9 to 2.7; p < 0.001) after surgery. CONCLUSIONS Additional post-operative NP measurement enhanced risk stratification for the composite outcomes of death or nonfatal myocardial infarction at 30 days and ≥180 days after noncardiac surgery compared with a pre-operative NP measurement alone.

Mechanism, glasgow coma scale, age, and arterial pressure (MGAP): a new simple prehospital triage score to predict mortality in trauma patients

Objectives:Prehospital triage of trauma patients is of paramount importance because adequate trauma center referral improves survival. We developed a simple score that is easy to calculate in the prehospital phase. Design:Multicenter prospective observational study. Setting:Prehospital physician-staffed emergency system in university and nonuniversity hospitals. Interventions:We evaluated 1360 trauma patients receiving care from a prehospital mobile intensive care unit in 22 centers in France during 2002. The association of prehospital variables with in-hospital death was tested using logistic regression, and a simple score (the Mechanism, Glasgow coma scale, Age, and Arterial Pressure [MGAP] score) was created and compared with the triage Revised Trauma Score, Revised Trauma Score, and Trauma Related Injury Severity Score. The model was validated in 1003 patients from 2003 through 2005. Measurements and Main Results:Four independent variables were identified, and each was assigned a number of points proportional to its regression coefficient to provide the MGAP score: Glasgow Coma Scale (from 3–15 points), blunt trauma (4 points), systolic arterial blood pressure (>120 mm Hg: 5 points, 60 to 120 mm Hg: 3 points), and age <60 yrs (5 points). The area under the receiver operating characteristic curve of MGAP was not significantly different from that of the triage Revised Trauma Score or Revised Trauma Score, but when sensitivity was fixed >0.95 (undertriage of 0.05), the MGAP score was more specific and accurate than triage Revised Trauma Score and Revised Trauma Score, approaching those of Trauma Related Injury Severity Score. We defined three risk groups: low (23–29 points), intermediate (18–22 points), and high risk (<18 points). In the derivation cohort, the mortality was 2.8%, 15%, and 48%, respectively. Comparable characteristics of the MGAP score were observed in the validation cohort. Conclusion:The MGAP score can accurately predict in-hospital death in trauma patients.

Prognostic Significance of Blood Lactate and Lactate Clearance in Trauma Patients

Background:Lactate has been shown to be a prognostic biomarker in trauma. Although lactate clearance has already been proposed as an intermediate endpoint in randomized trials, its precise role in trauma patients remains to be determined. Methods:Blood lactate levels and lactate clearance (LC) were calculated at admission and 2 and 4 h later in trauma patients. The association of initial blood lactate level and lactate clearance with mortality was tested using receiver-operating characteristics curve, logistic regression using triage scores, Trauma Related Injury Severity Score as a reference standard, and reclassification method. Results:The authors evaluated 586 trauma patients (mean age 38 ± 16 yr, 84% blunt and 16% penetrating, mortality 13%). Blood lactate levels at admission were elevated in 327 (56%) patients. The lactate clearance should be calculated within the first 2 h after admission as LC0–2 h was correlated with LC0–4 h (R2 = 0.55, P < 0.001) but not with LC2–4 h (R2 = 0.04, not significant). The lactate clearance provides additional predictive information to initial blood lactate levels and triage scores and the reference score. This additional information may be summarized using a categorical approach (i.e., less than or equal to −20 %/h) in contrast to initial blood lactate. The results were comparable in patients with high (5 mM/l or more) initial blood lactate. Conclusions:Early (0–2 h) lactate clearance is an important and independent prognostic variable that should probably be incorporated in future decision schemes for the resuscitation of trauma patients.

Statin Therapy within the Perioperative Period

STATINS are highly effective in lowering serum cholesterol concentrations through 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibition and thus are central to the primary and secondary prevention of cardiovascular disease. More than 50% of patients undergoing major vascular surgery and 80% undergoing cardiac surgery are on chronic statin therapy. 1,2 Statins also exert numerous lipid-independent or “pleiotropic” effects (effects that were not expected during drug development) as a result of their ability to inhibit the inflammatory response, reduce thrombosis, enhance fibrinolysis, decrease platelet reactivity, inhibit cell growth, reduce ischemia–reperfusion injury, and restore endothelial function. These beneficial effects result predominantly from the modulation of the complex interplay between the pathologic triad of inflammation, dynamic obstruction, and thrombosis. 3 This triad is integral to the surgical stress response and central to postoperative outcomes. However, recent reports noted that patients who undergo postoperative statin withdrawal experience increased cardiac morbidity when compared with patients who undergo early postoperative readministration of statins or with patients not treated with statins. 1,4 These facts raise several important questions for the anesthesiologist regarding statin therapy during the perioperative period: (1) Do statins modify perioperative risk? (2) Is continuation or discontinuation of statin therapy during the perioperative period associated with additional risk? (3) Do the potential benefits of statin therapy outweigh the potential risks? This review of the literature explores the risks and benefits associated with perioperative statin therapy.

Postoperative Admission to a Dedicated Geriatric Unit Decreases Mortality in Elderly Patients with Hip Fracture

Background Elderly patients with hip fracture have a 5 to 8 fold increased risk of death during the months following surgery. We tested the hypothesis that early geriatric management of these patients focused on co-morbidities and rehabilitation improved long term mortality. Methods and Findings In a cohort study over a 6 year period, we compared patients aged >70 years with hip fracture admitted to orthopedic versus geriatric departments in a time series analysis corresponding to the creation of a dedicated geriatric unit. Co-morbidities were assessed using the Cumulative Illness Rating Scale (CIRS). Each cohort was compared to matched cohorts extracted from a national registry (n = 51,275) to validate the observed results. Main outcome measure was 6-month mortality. We included 131 patients in the orthopedic cohort and 203 in the geriatric cohort. Co-morbidities were more frequent in the geriatric cohort (median CIRS: 8 vs 5, P<0.001). In the geriatric cohort, the proportion of patients who never walked again decreased (6% versus 22%, P<0.001). At 6 months, re-admission (14% versus 29%, P = 0.007) and mortality (15% versus 24%, P = 0.04) were decreased. When co-morbidities were taken into account, the risk ratio of death at 6 months was reduced (0·43, 95%CI 0·25 to 0·73, P = 0.002). Using matched cohorts, the average treatment effects on the treated associated to early geriatric management indicated a reduction in hospital mortality (−63%; 95% CI: −92% to −6%, P = 0.006). Conclusions Early admission to a dedicated geriatric unit improved 6-month mortality and morbidity in elderly patients with hip fracture.

Influence of renal dysfunction on the accuracy of procalcitonin for the diagnosis of postoperative infection after vascular surgery.

Objective:Procalcitonin has been advocated as a specific biomarker for bacterial infection. We performed this study to determine whether accuracy of procalcitonin for diagnosis of postoperative bacterial infection is affected by renal function after aortic surgery. Design:Single-center prospective study. Setting:University hospital. Patients:Two hundred seventy-six patients scheduled for elective major aortic surgery. Interventions:Blood samples were taken before surgery and each day over the 5-day postoperative period, and measurement of serum procalcitonin was performed. Diagnosis of infection was performed by a blinded expert panel. Renal function was assessed using an estimate of creatinine clearance with the Cockcroft formulas. Renal dysfunction was defined as a creatinine clearance <50 mL·min−1. Measurements and Main Results:Infection was diagnosed in 67 patients. Seventy five patients (27%) had postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, with a peak reached at the fourth postoperative day, but it was significantly higher in patients with impaired renal function in both control and infected patients. The optimal threshold of procalcitonin markedly differed in patients with renal dysfunction compared with patients without renal dysfunction (2.57 vs. 0.80 ng·mL−1, p < .05). The diagnostic accuracy of procalcitonin significantly increased (0.74 vs. 0.70, p < .05) when the threshold of procalcitonin was adapted to the renal function. The elevation of procalcitonin occurred 2 days before the medical team was able to diagnose infection. Conclusions:Procalcitonin is a valuable marker of bacterial infections after major aortic surgery, but renal function is a major determinant of procalcitonin levels and thus different thresholds should be applied according to renal function impairment.