Alain Edouard

Prospective, randomized trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients

OBJECTIVES To compare the efficacy of a newly available antiseptic solution (composed of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, and 4% benzyl alcohol), with 10% povidone iodine, on the prevention of central venous or arterial catheter colonization and infection. DESIGN Prospective, randomized clinical trial. SETTING Surgical-trauma intensive care unit (ICU) in a university hospital. PATIENTS All patients admitted to the ICU and requiring the insertion of a central venous and/or an arterial catheter from July 1, 1992 to October 31, 1993. INTERVENTIONS Patients were randomly assigned to one of two groups according to the antiseptic solution used for insertion and catheter care. The same solution was used for skin disinfection from the time of catheter insertion to the time of removal of each catheter. MEASUREMENTS AND MAIN RESULTS Catheter distal tips were quantitatively cultured when catheters were no longer necessary, if there was a suspicion of catheter-related infection, and routinely after 7 days of use for arterial catheters, or after 15 days of use for central venous catheters. The rate of significant catheter colonization (i.e., > or = 10(3) colony-forming units [cfu]/mL by quantitative culture), and catheter-related sepsis (as defined by sepsis abating following catheter removal per 1,000 catheter-days), were significantly lower in the chlorhexidine group (12 vs. 31 [relative risk 0.4, 95% confidence interval 0.1 to 0.9, p < .01] and 6 vs. 16 [relative risk 0.4, 95% confidence interval 0.1 to 1, p = 0.5], respectively). The rate of central venous catheter colonization and central venous catheter-related sepsis per 1,000 catheter-days were also significantly lower in the chlorhexidine group (8 vs. 31 [relative risk 0.3, 95% confidence interval 0.1 to 1, p = .03] and 5 vs. 19 [relative risk 0.3, 95% confidence interval 0.1 to 1, p = .02], respectively). Finally, the rate of arterial catheter colonization per 1,000 catheter-days was significantly lower in the chlorhexidine group (15 vs. 32 [relative risk 0.5, 95% confidence interval 0.1 to 1, p = .05]), whereas the rate of arterial catheter-related sepsis per 1,000 catheter-days was similar for the two study groups (8 in the chlorhexidine group vs. 10 in the povidone iodine group [relative risk 0.8, 95% confidence interval 0.1 to 2.2, p = .6]). The 0.25% chlorhexidine solution was superior to the 10% povidone iodine solution in preventing catheter colonizations and catheter-related sepsis due to Gram-positive bacteria (5 vs. 20 [p < .001], and 2 vs. 10 [p < .001], respectively), whereas the activity of the 0.25% chlorhexidine solution was nonsignificantly superior in preventing Gram-negative infections (7 vs. 4 [p = .5], and 4 vs. 2 [p = .8], respectively). CONCLUSIONS The 4% alcohol-based solution of 0.25% chlorhexidine gluconate and 0.025% benzalkonium chloride was more effective than 10% povidone iodine for insertion site care of short-term central venous and arterial catheters. This effect appeared related to a more efficacious prevention of infections with Gram-positive bacteria.

Procalcitonin and C-reactive protein during the early posttraumatic systemic inflammatory response syndrome

Objectives: To describe the initial evolution of serum procalcitonin (PCT) and C-reactive protein (CRP) in previously healthy adult trauma patients and to compare the relationship of the expression of these two proteins with indicators of trauma severity. Design: Prospective, descriptive, longitudinal study.Setting: Surgical ICU in an university hospital.Patients: Twenty-one patients admitted during the first posttraumatic 3 h exhibiting an Injury Severity Score (ISS) between 16 and 50 were enrolled.Measurements: Blood sampling was performed on admission and on posttraumatic days 0.5,1, 2 and 3 to assess serum levels of PCT and CRP. Total creatine kinase (CKtot) and lactate dehydrogenase (LDHtot) activities in the serum were used as tissue damage indicators.Results: PCT exhibited an early and transient increase in serum levels similar to a more delayed change of CRP levels. Peak PCT and peak CRP were related to the ISS, the extent of tissue damage and the amount of fluid replacement during the first day. During the first 3 posttraumatic days, 90 % of the patients exhibited a generalized inflammatory syndrome without infection.Conclusions: An early and transient release of PCT into the circulation was observed after severe trauma and the amount of circulating PCT seemed proportional to the severity of tissue injury and hypovolemia, yet unrelated to infection. The predictive value of both PCT and CRP for a forthcoming multiple organ failure still remains to be clarified.

Early embolization and vasopressor administration for management of life-threatening hemorrhage from pelvic fracture.

BACKGROUND In this retrospective study, we reviewed our protocol for management of hemodynamically unstable patients with pelvic injury. METHODS We managed the patients with the same predetermined plan including controlled hemodynamic resuscitation with early use of vasopressors and pelvic angiography as a first-line treatment. RESULTS Of 311 patients with pelvic fracture, 32 hemodynamically unstable patients (10.3%) underwent pelvic angiography, which was followed by embolization in 25 cases. Angiography was successful for 24 patients (96%) and extrapelvic bleeding was diagnosed in 5 patients (15%). Three of six laparotomies performed before angiography were nontherapeutic. One of seven laparotomies performed after angiography was negative. CONCLUSION A protocol for management of patients with pelvic injury and hemodynamic instability that is associated with controlled resuscitation including vasopressor and early pelvic angioembolization is effective for treating pelvic hemorrhage and diagnosing extrapelvic hemorrhage. Further studies are needed to confirm the respective place of angiographic and surgical control of bleeding.

Influence of Venous Return on Baroreflex Control of Heart Rate during Lumbar Epidural Anesthesia in Humans

The role of variation of venous return on baroreflex control of heart rate during lumbar epidural anesthesia was investigated in 12 unpremedicated patients. Group 1 patients (n = 6) received 8 ml of 0.5% plain bupivacaine in the epidural space (L3–4) (mean upper level of analgesia at T10). Group 2 patients (n = 6) received 8 ml of saline at the same level in the epidural space. Following the epidural injection, phenylephrine (PHE) and nitroglycerin (NTG) were employed to alter the stimulation of baroreceptor sites before and during application of lower body positive pressure (LBPP). Plasma bupivacaine, catecholamines, renin activity, and vasopressin were assayed. In contrast to saline, epidural bupivacaine induced a decrease in systolic arterial and right atrial pressures (−11 ‡ 4 and −3.2 ‡ 0.7 mmHg, respectively, mean ‡ SEM) without change in heart rate, an increase in baroreflex slopes during PHE and NTG injections (+5.9 ‡ 1.6 ms/mmHg and +2.8 ‡ 0.9 ms/mmHg, respectively), and a decrease in plasma norepinephrine (−248 ‡ 89 pg/ml). The application of LBPP restored hemodynamic and reflex variables to preepidural analgesia values, whereas plasma catecholamines decreased further. Plasma renin activity and vasopressin were not modified at any time in either groups. This study indicates that lumbar epidural anesthesia enhances cardiac vagal tone mainly through a decrease in venous return.

The Influence of Tidal Volume on the Dynamic Variables of Fluid Responsiveness in Critically Ill Patients

Respiratory-related variabilities in stroke volume and arterial pulse pressure (&Dgr;%Pp) are proposed to predict fluid responsiveness. We investigated the influence of tidal volume (Vt) and adrenergic tone on these variables in mechanically ventilated patients. Cyclic changes in aortic velocity–time integrals (&Dgr;%VTIAo, echocardiography) and &Dgr;%Pp (catheter) were measured simultaneously before and after intravascular volume expansion, and Vt was randomly varied below and above its basal value. Intravascular volume expansion was performed by hydroxyethyl starch (100 mL, 60 s). Receiver operating characteristic curves were generated for &Dgr;%VTIAo, &Dgr;%Pp and left ventricle cross-sectional end-diastolic area (echocardiography), considering the change in stroke volume after intravascular volume expansion (≥15%) as the response criterion. Covariance analysis was used to test the influence of Vt on &Dgr;%VTIAo and &Dgr;%Pp. Twenty-one patients were prospectively included; 9 patients (43%) were responders to intravascular volume expansion. &Dgr;%VTIAo and &Dgr;%Pp were higher in responders compared with nonresponders. Predictive values of &Dgr;%VTIAo and &Dgr;%Pp were similar (threshold: 20.4% and 10.0%, respectively) and higher than that of left ventricle cross-sectional end-diastolic area at the appropriate level of Vt. &Dgr;%Pp was slightly correlated with norepinephrine dosage. &Dgr;%Pp increased with the increase in the level of Vt both before and after intravascular volume expansion, contrasting with an unexpected stability of &Dgr;%VTIAo. In conclusion, &Dgr;%VTIAo and &Dgr;%Pp are good predictors of intravascular fluid responsiveness but the divergent evolution of these two variables when Vt was increased needs further explanation.

Cortisol response to corticotropin stimulation in trauma patients: influence of hemorrhagic shock.

Background An abnormal adrenocortical function and a vasopressor dependency have been demonstrated during septic shock. Because trauma and hemorrhage are the leading causes of noninfectious inflammatory syndromes, the goal of this study was to assess the adrenal reserve of trauma patients and its relation with clinical course. Methods Cortisol response to an intravenous corticotropin bolus was obtained in 34 young trauma patients (Injury Severity Score =29.1 ± 7.3) at the end of the resuscitative period (“early phase”) and at the end of the first posttraumatic week (“late period”). Cortisol response less than +9 g/dl defined an impaired adrenal function, and the corresponding patient was called a nonresponder. According to the early response, hemorrhagic shock, circulating interleukin-6, need for vasopressor therapy, subsequent organ dysfunction and infection, and outcomes were studied. Results Sixteen patients (47%) were nonresponders at the end of the early phase. Hemorrhagic shock was more frequent (69 vs. 28%;P = 0.037) and interleukin-6 concentrations were higher (728 ± 589 vs. 311 ± 466 pg/ml;P = 0.048) in these patients. The early cortisol responses were negatively correlated with the concomitant interleukin-6 serum concentrations (r2 = 0.298;P = 0.003). Four early nonresponders (and shock patients) remained nonresponders during the late phase (25%). Morbidity and mortality were similar in early nonresponders and responders. The duration of norepinephrine treatment and the total amount of infused drug were significantly higher in early nonresponders. Conclusions A sustained impairment of adrenal reserve is frequently observed in trauma patients. This abnormal cortisol response to corticotropin stimulation is related with the inflammatory consequences of hemorrhagic shock and is followed by a prolonged vasopressor dependency.

Comparative ventricular electrophysiologic effect of racemic bupivacaine, levobupivacaine, and ropivacaine on the isolated rabbit heart

BACKGROUND Numerous local anesthetics have an asymmetric tetrahedron carbon, which confers stereoselective differences between the isomers. The authors attempted to quantify the depressant effect of racemic bupivacaine, levobupivacaine, and ropivacaine on myocardial ventricular conduction and on myocardial contractility. METHODS The authors studied the pharmacokinetics (outflow concentration) and pharmacodynamics (QRS widening) of the three drugs infused in an isolated rabbit heart preparation. All data were fitted simultaneously with use of mixed-effect modeling, thus allowing precise statistical comparison between the three drug parameters. The rate dependence of QRS widening was fitted separately. RESULTS Racemic bupivacaine, levobupivacaine, and ropivacaine induced a calculated maximum increase in QRS duration in the ratio 1:0.4:0.3. Css50, the dose which caused half the maximum increase in QRS duration at steady state, was similar for all three drugs (22 micrometer free concentration). A rate dependence of QRS widening was observed, which was in the ratio 1:0.5:0.25 for racemic bupivacaine, levobupivacaine, and ropivacaine, respectively. CONCLUSIONS In the isolated rabbit heart, racemic bupivacaine, levobupivacaine, and ropivacaine induce an increase in QRS duration in the respective ratio of 1:0.4:0.3, which was rate dependent in approximately the same ratio.

Circulating cardiac troponin I in trauma patients without cardiac contusion

Objectives: To describe the evolution and the diagnostic value of cardiac troponin I (cTnI) and to relate its concentrations with the indicators of injury in trauma patients.Design: Prospective, observational study of 17 young, previously healthy, mechanically-ventilated patients during the early post-traumatic period in the Surgical ICU of a University Hospital.Methods: Serial measurements of serum cTnI, total creatine kinase activity (CKtot) and its isoenzyme MB (CK-MB) (on admission, 12 h later, then daily for 7 days), clinical data and repeated electrocardiographic (ECG) and transesophageal echocardiography (TEE) recordings.Results: Rhabdomyolysis was observed in all the patients with a significant relationship between CK-MB and CKtot. Despite the fact that no patient demonstrated ECG or TEE signs of myocardial contusion, elevated serum levels of cTnI were observed in six patients (35%) without obvious dilutional interference. As compared with the others, these patients exhibited a more frequent arterial hypotension (83% vs 18%, p=0.035), required greater volume expansion on day 1 (22,000 vs 8,500 ml, p=0.027) and usually demonstrated early (83% vs 9%, p=0.005) and late (66% vs 9%, p=0.028) multiple organ dysfunction syndrome.Conclusions: Taking into account the high reported sensitivity and specificity of cTnI dosage, the present results suggest cTnI can play a role in the evaluation of indirect myocardial injury following traumatic shock.

Pharmacokinetics and absolute bioavailability of ciprofloxacin administered through a nasogastric tube with continuous enteral feeding to critically ill patients

Objective: To determine the pharmacokinetics and absolute bioavailability of ciprofloxacin in 12 critically ill patients receiving continuous enteral feeding. Design: a prospective, cross-over study. Setting: 12-bed surgical intensive care unit in a University Hospital. Patients: 12 stable critically ill patients on mechanical ventilation and receiving continuous enteral feeding (Normoréal fibres) without diarrhea or excessive residual gastric contents ( < 200 ml/4 h). None had gastro-intestinal disease, renal insufficiency (estimated creatinine clearance ≥ 50 ml/min) or was receiving medications that could interfere with ciprofloxacin absorption or metabolism. Measurements and main results: The study was carried out after the fourth (steady state) b. i. d. intravenous (i. v.) 1-h infusion of 400 mg and the second b. i. d. nasogastric (NG) dose of 750 mg (crushed tablet in suspension). Plasma concentrations were measured by high-performance liquid chromatography. The median (range) peak concentration after i. v. infusion was 4.1 (1.5–7.4) mg/l, and that after NG administration was 2.3 (0.7–5.8) mg/l, occurring 1.25 (0.75–3.33) h after dosing. The median [range] areas under plasma concentration-time curves were similar for the two administration routes (10.3 [3.3–34.6] and 8.4 [3.6–53.4] for i. v. infusion and NG administration, respectively). Ciprofloxacin bioavailability ranges from 31 to 82 % (median, 44 %). Conclusions: In tube-fed critically ill patients, a switch to the NG ciprofloxacin after initial i. v. therapy to simplify the treatment of severe infections is restricted to those for whom serial assessments of ciprofloxacin levels are routinely available.

Incidence and Significance of Cardiac Troponin I Release in Severe Trauma Patients

Background:The incidence and significance of troponin I release and its mechanism are unknown in severe trauma patients. The characteristics of this release were prospectively studied in such patients and correlated with presence of shock, existence of myocardial contusion, and outcome. Methods:During a 24-month period, serial electrocardiogram recordings and troponin I measurements were performed in all trauma patients admitted at a surgical intensive care unit. The diagnosis of a significant myocardial contusion was made on electrocardiographic criteria. According to the time course of troponin I, three groups of patients were defined a priori: very transient (≤ 12 h) and limited release (troponin I < 2 &mgr;g/l), transient (≤ 36 h) and significant release (troponin I ≥ 2 &mgr;g/l), and sustained (> 36 h) and significant release (troponin I > 2 &mgr;g/l). In the last group, coronary artery angiography was performed. Results:The incidence of troponin I release was 12% (95% confidence interval [CI], 9.6–14.4%) in 728 patients. A significant myocardial contusion was found in 35 patients (5%; 95% CI, 3.4–6.6%) and may occur in the absence of chest trauma and without troponin I release. Sensitivity, specificity, and positive and negative predictive values of troponin I for the diagnosis of myocardial contusion were 63, 98, 40, and 98%, respectively. Troponin I release was observed in 54 early (> 48 h) survivors (7%; 95% CI, 5.6–9.6%) without preexisting coronary artery disease. A sustained and significant release of troponin I (17 patients) was frequently associated with chest trauma (82%) and constantly with electrocardiographic abnormalities. A coronary artery injury was found in 7 patients (2 major and 5 minor vascular injuries) (1% of the whole group; 95% CI, 0.4–2.0%). Mortality was similar in early survivors with (15%; 95% CI, 7–27%) or without (12%; 95% CI, 9–14%) troponin I release. The odds ratio for late mortality was 1.32 (95% CI, 0.61–2.85) in patients with troponin I release. Conclusions:Serial electrocardiogram recordings and troponin I assessments may be proposed for initial screening in high-risk trauma patients to detect anatomical cardiac injuries through the time course of circulating protein. Troponin I release does not have a prognosis value in trauma patients.