Comparison of two versions of the Vigileo-FloTrac system (1.03 and 1.07) for stroke volume estimation: a multicentre, blinded comparison with oesophageal Doppler measurements.

BACKGROUND: Our aim was to evaluate the validity of stroke volume measurements obtained using the Vigileo-FloTrac system in comparison with those obtained using oesophageal Doppler considered as a reference. METHODS: Prospective, multicentre study (four university hospitals), in which investigators were blinded to stroke volume values acquired simultaneously with the other technique. Two different versions of the Vigileo software (1.03 and 1.07) were studied and compared over two consecutive periods of time. Forty critically ill patients (three ICUs) and 20 high-risk surgical patients (one operating theatre) were studied over a 6-month period. RESULTS: Two hundred and forty paired stroke volume values obtained using the second version of the Vigileo (1.07) yielded better correlation and agreement (R=0.48, P<0.001; bias=4 ml, limits of agreement: +/- 41 ml) than the 207 paired values obtained using version 1.03 (R=0.12, P=0.1; bias=1 ml, limits of agreement: +/- 75 ml). However, even with the second version, the percentage error in stroke volume measurement was 58%, a value still above the range considered clinically acceptable (30%). CONCLUSIONS: The precision of stroke volume estimation using Vigileo-FloTrac has improved with the second version of the software (1.07), but remains insufficient to allow the replacement of the reference technique in the population studied.

[Recombinant activated factor VII as a life-saving therapy for severe postpartum haemorrhage unresponsive to conservative traditional management]. / Intérêt du facteur VII activé recombinant dans l'hémorragie de la délivrance sévère réfractaire à la prise en charge conservatrice conventionnelle.

Postpartum haemorrhage remains the main cause of maternal morbidity and mortality. Treatment aims at maintaining hemodynamic circulation and preventing shock by stopping blood loss both medically and surgically. We report two cases of major postpartum haemorrhage due to uterine atony. Patients developed haemorrhagic shock and severe coagulation disorders (nadir values of PTT were <10% and fibrinogen was <0.1 g/l). Well-codified medical (ocytocin, sulprostone) and surgical management (ligation of both hypogastic arteries in the two cases completed by staged uterine ligation in one case) failed to stop bleeding. Recently, several case reports described successful use of recombinant activated factor VII (rFVIIa) in scheduled surgery, trauma and major postpartum haemorrhage. Thus, after transfusion of more than one blood mass and failure of surgical haemostasis to stop bleeding, rFVIIa (60 microg/kg) was given. A single iv bolus injection stopped ongoing diffuse haemorrhage in the two cases. No further transfusion was required afterwards in both patients. RFVIIa might thus be a strong complementary agent in the management of major postpartum haemorrhage. Optimal dose, timing and safety characteristics of rVIIa administration remain to be determined. One patient developed four weeks later thrombosis of both ovarian veins, a complication that can be related to either rFVIIa or to the staged uterine ligations performed during surgery.

Sedation, sucralfate, and antibiotic use are potential means for protection against early-onset ventilator-associated pneumonia.

To examine risk factors for early-onset ventilator-associated pneumonia (EOP) in patients requiring mechanical ventilation (MV), we performed a prospective cohort study that included 747 patients. Pneumonia was defined as a positive result for a protected quantitative distal sample. EOP was defined as pneumonia that occurred from day 3 to day 7 of MV. Eighty patients (10.7%) experienced EOP. Independent predictors of EOP were male sex (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.18-3.63), actual Glasgow Coma Scale value of 6-13 (OR, 1.95; 95% CI, 1.2-3.18), high Logistic Organ Dysfunction score at day 2 (OR, 1.12 per point; 95% CI, 1.02-1.23), unplanned extubation (OR, 3.19; 95% CI, 1.28-7.92), and sucralfate use (OR, 1.81; 95% CI, 1.01-3.26). Protection occurred with use of aminoglycosides (OR, 0.36; 95% CI, 0.17-0.76), beta -lactams and/or beta -lactamase inhibitors (OR, 0.47; 95% CI, 0.28-0.83), or third-generation cephalosporins (OR, 0.33; 95% CI, 0.16-0.74). Sucralfate use and unplanned extubation are independent risk factors for EOP. Use of aminoglycosides, beta-lactams/ beta-lactamase inhibitors, or third-generation cephalosporins protects against EOP.

Mechanical and electrophysiological effects of thiopental on rat cardiac left ventricular papillary muscle.

Thiopental induces a negative inotropic effect on mammalian heart muscle, where it decreases Ca2+ current and Ca2+ release from the sarcoplasmic reticulum and reduces K+ currents. We analysed the effects of thiopental on the mechanical and electrical activities of rat myocardium, which differ markedly from those of other mammals. The effects of thiopental on mechanical parameters and on the transmembrane resting (RP) and action (AP) potentials of rat left ventricular papillary muscle were investigated. These effects were also studied in the presence of atenolol, a beta-blocking agent, and 4-aminopyridine (4-AP), a blocker of the transient outward K+ current. Thiopental (3.8 x 10(-6), 3.8 x 10(-5) and 1.1 x 10(-4) M) induced a dose-dependent positive inotropic effect. This positive inotropic effect persisted in the presence of atenolol (1 x 10(-6) M) but did not develop in the presence of 1 mM 4-AP; 4-AP had a positive inotropic effect but not in the presence of thiopental. Moreover, thiopental (3.8 x 10(-5) M) lengthened the plateau and the slow repolarizing phase of the AP, while 1 mM 4-AP only prolonged the plateau duration. In rat myocardium, the positive inotropic effect of thiopental in part mimics that of 4-AP, and in part may be explained by the lengthening of the slow repolarizing phase of the AP.

Effects of halothane on the membrane potential in skeletal muscle of the frog.

Halothane has many effects on the resting membrane potential (V(m)) of excitable cells and exerts numerous effects on skeletal muscle one of which is the enhancement of Ca(2+) release by the sarcoplasmic reticulum (SR) resulting in a sustained contracture. The aim of this study was to analyse the effects of clinical doses of halothane on V(m), recorded using intracellular microelectrodes on cleaned and non stimulated sartorius muscle which was freshly isolated from the leg of the frog Rana esculenta. We assessed the mechanism of effects of superfused halothane on V(m) by the administration of selective antagonists of membrane bound Na(+), K(+) and Cl(-) channels and by inhibition of SR Ca(2+) release. Halothane (3%) induced an early and transient depolarization (4.5 mV within 7 min) and a delayed and sustained hyperpolarization (about 11 mV within 15 min) of V(m). The halothane-induced transient depolarization was sensitive to ryanodine (10 microM) and to 4-acetamido-4'-isothiocyanatostilbene 2,2' disulphonic acid (SITS, 1 mM). The hyperpolarization of V(m) induced by halothane (0.1 - 3%) was dose-dependent and reversible. It was insensitive to SITS (1 mM), tetrodotoxin (0.6 microM), and tetraethylammonium (10 mM) but was blocked and/or prevented by ryanodine (10 microM), charybdotoxin (CTX, 1 microM), and glibenclamide (10 nM). Our observations revealed that the effects of halothane on V(m) may be related to the increase in intracellular Ca(2+) concentration produced by the ryanodine-sensitive Ca(2+) release from the SR induced by the anaesthetic. The depolarization may be attributed to the activation of Ca(2+)-dependent Cl(-) (blocked by SITS) channels and the hyperpolarization to the activation of large conductance Ca(2+)-dependent K(+) channels, blocked by CTX, and to the opening of ATP-sensitive K(+) channels, inhibited by glibenclamide.

[Organ procurement from cardiac arrest donors: outcome of kidney grafts and recommendations]. / Prélèvements d'organes sur donneurs décédés à coeur arrêté: devenir des greffons rénaux, propositions.

OBJECTIVES: To compare literature data with results obtained with organs procured from donors who died from cardiac arrest and to make proposals for this mode of organ procurement in France. METHODS: Over the last 10 years, 10 organ donors (2%) among a series of 486 donors in a state of brain death, had died of cardiac arrest. The arrest were perfused with double-balloon catheters. The outcome of the subsequent kidney grafts was compared with data in the literature. RESULTS: Fifteen of the 18 kidneys from cardiac arrest donors were functioning 1 month after implantation compared with 17 of the 20 kidneys from braindeath donors with beating hearts. The rate of acute tubular necrosis was 55% in the cardiac arrest kidneys and 40% in the beating-heart kidneys. Serum creatinine at 1 yeart was 145 +/- 69 mumol/l 17 +/- 29 mumol/l respectively. DISCUSSION: These results and those reported in the literature demonstrate that kidney procurement from cardiac arrest donors is feasible. If intensive care and surgery units are well organized, this type of organ procurement could provide a larger number of organs for transplantation. Emergency teams must be available for preparing and transferring the organs.

Assessment of gastric mucosal perfusion during simulated hypovolemia in healthy volunteers.

We described here an original device for laser Doppler (LD) flowmetry measurements of gastric mucosal perfusion, which was used here in healthy volunteers. A modified nasogastric tube containing the LD probe was inserted. Aspiration via a catheter, fixed in parallel to the probe, held the probe against the gastric wall. This new device was used to assess gastric mucosal perfusion in seven volunteers during simulated hypovolemia induced by lower body negative pressure (LBNP) application. The LBNP consisted of three successive levels of depression (-10, -20, and -30 mm Hg). Although mean arterial pressure remained unchanged during negative pressure application, there was a significant decrease in cardiac output (transthoracic electrical impedance) at each stage of LBNP. In contrast, gastric mucosal perfusion decreased significantly only at higher level of sympathetic stimulation corresponding to unloading of both cardiopulmonary and arterial baroreflexes (-30 mm Hg). It may be hypothetized that local vascular mechanisms exist to maintain gastric mucosal perfusion during moderate sympathetic stimulation induced by selective unloading of cardiopulmonary receptors. In the healthy volunteers studied, we found that LD flowmetry is a valuable tool to evaluate gastric mucosal perfusion when the probe is maintained in a constant position by the technique described here.

Left ventricular function after severe trauma.

OBJECTIVE: To evaluate cardiac function at the early phase of severe trauma. DESIGN: Prospective, clinical study. SETTING: Anesthesiological Intensive Care Unit. PATIENTS: 7 consecutive patients admitted after severe trauma (ISS: 38 +/- 9, mean +/- SD), without preexisting cardiac disease. INTERVENTIONS: Each patient received midazolam and sufentanyl for sedation. Right heart catheterization (Swan-Ganz) and transesophageal echocardiography (TEE) were performed. The fractional area change (FAC) of the left ventricle was calculated within 6 h following trauma and at day 1 and day 2 in order to evaluate left ventricular function. MEASUREMENTS AND RESULTS: All of the patients had a low FAC value < 50% at day 0 (43.2 +/- 2.4%, range 39-46%), which increased significantly at day 2 (52.5 +/- 4%, range 47-59%, p = 0.001), whereas heart rate and preload (assessed by left ventricular end diastolic area and pulmonary arterial occlusion pressure) were constant and afterload, assessed by systolic blood pressure, increased significantly between day 0 and day 2 (112 +/- 21 to 145 +/- 24 mmHg, p = 0.02). CONCLUSION: The initial phase of severe trauma is associated with an abnormal cardiac function, suggested by a low FAC value. This myocardial dysfunction must be taken into account for early resuscitation after severe injury.

Transgastric, pulsed Doppler echocardiographic determination of cardiac output.

OBJECTIVE: The aim of this study was to evaluate the accuracy of cardiac output measurement with transesophageal echocardiography (TEE) using a transgastric, pulsed Doppler method in acutely ill patients. DESIGN: Cardiac output was simultaneously measured by thermodilution (TD) and a transgastric, pulsed Doppler method. SETTING: The study was carried out in a surgical intensive care unit as part of the management protocol of the patients. PATIENTS: Thirty consecutive acutely ill patients with a Swan-Ganz catheter, mechanically ventilated, sedated and with a stable hemodynamic condition were included. MEASUREMENTS: Pulsed Doppler TEE was performed using a transgastric approach in order to obtain a long axis view of the left ventricle. Cardiac output was calculated from the left ventricular outflow tract diameter, the velocity time integral of the blood flow profile and heart rate. RESULTS: One patient was excluded because of the presence of aortic regurgitation and another, because of the impossibility of obtaining a transgastric view. Twenty-eight simultaneous measurements were performed in 28 patients. A clinically acceptable correlation and agreement were found between the two methods (Doppler cardiac output = 0.889 thermodilution cardiac output +0.74 l/min, r = 0.975, p <0.0001). CONCLUSION: Transgastric pulsed Doppler measurement across the left ventricular outflow tract with TEE is a very feasible and clinically acceptable method for cardiac output measurement in acutely ill patients.

Role of systemic inflammatory response syndrome and infection in the occurrence of early multiple organ dysfunction syndrome following severe trauma.

OBJECTIVE: To evaluate the role of infection and systemic inflammatory response syndrome (SIRS) on the occurrence of early posttraumatic MODS. DESIGN: Retrospective study. SETTING: University Teaching Hospital ICU. PATIENTS: 163 consecutive patients hospitalized for more than 48 hours following severe trauma. MEASUREMENTS AND MAIN RESULTS: The patients were classified into two groups in respect to the existence of MODS at day 2. There was 27 patients in the MODS group and 136 patients in the no MODS group. The two groups were similar with respect to age, sex ratio and Simplified Acute Physiology Score. The MODS group had a higher mortality (52 versus 7%), Injury Severity Score (45 +/- 14 versus 31 +/- 13), hypovolemic shock rate (74 versus 30%), massive volume replacement rate (59 versus 6%) and SIRS rate (81 versus 54%) than the no MODS group (P < 0.05). The rate of infection was similarly low in the MODS and no MODS group (4 versus 6% respectively). CONCLUSION: Early MODS is often associated with hypotension and massive volume administration but very rarely with infection, despite the high rate of SIRS.

Whole body oxygen uptake is not a good indicator of liver allograft function following orthotopic liver transplantation.

Variations of whole body oxygen uptake (VO2) have been studied during orthotopic liver transplantation. Some authors have suggested that the increase in VO2 after revascularization of the graft could be an index of good function of the grafted liver and thus low VO2 an early sign of primary non-function. The purpose of our study was to assess the temporal course of measured respiratory VO2 and to compare the VO2 changes to indicators of hepatic function. We used a metabolic monitor (Deltatrac, Datex Corp. Finland) to measure VO2 in 18 patients during transplantation. Clotting factors II and V at 1, 3, 7, 14 and 21 days post-operatively and peak serum transaminases within the first 3 post-operative days were determined. Variations of VO2 were a decrease during the anhepatic phase and an increase following the reperfusion phase as compared to the VO2 value obtained at the beginning of the procedure. No correlation was found between the increase in VO2 after reperfusion of the graft and either factor II (r = 0.33-0.4), factor V (r = 0.23-0.43) or peak transaminases (r = 0.13). One patient developed a primary non-function of the graft. For this patient VO2 increased far above the pre-anhepatic values. The authors conclude that VO2 is not a reliable sign of graft function.

Continuous monitoring of mixed venous oxygen saturation during orthotopic liver transplantation.

Hemodynamic management is an important issue concerning anesthesia for orthotopic liver transplantation (OLT). Mixed venous oxygen saturation (SvO2) is considered a good index of tissue oxygenation, but controversy exists about the usefulness of monitoring this parameter in different types of surgery. Therefore, a prospective study was performed to determine changes in SvO2 during OLT and to study the correlation between SvO2 and hemodynamic measurements. Thirty patients undergoing transplantation for end-stage liver disease were divided into two groups: group 1 (n = 15, aged 42 +/- 11 years [mean +/- SD]) without venovenous bypass (VVB), and group 2 (n = 15, aged 43 +/- 10 years) with VVB. SvO2 was greater than 74% throughout the procedure and remained stable during dissection and the anhepatic phase. There was a significant increase in SvO2 after unclamping the portal vein in group 1, whereas a significant decrease was observed during the first hour following reperfusion in group 2. There was no correlation among SvO2 and oxygen consumption, arterial oxygen saturation, (SaO2), or hemoglobin concentrations. A statistically significant correlation was found between SvO2 and cardiac index in both groups (group 1: r = 0.58, P = 0.01; group 2: r = 0.51, P = 0.01), but the correlation was relatively poor. Continuous monitoring of SvO2 may be useful, but cannot substitute for intermittent determinations of other hemodynamic or oxygenation parameters.

A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer.

A significant increase in the dose intensity of chemotherapy with fluoropyrimidines and platinum complexes has resulted from selective circadian timing and/or circadian modulation of the infusion rate. The relevance of such chronopharmacologic strategy for improving the outcome of metastatic colorectal cancer was evaluated in an extended Phase II clinical trial involving 93 patients. Of these, 49% previously had received chemotherapy and/or radiation therapy. The drugs 5-fluorouracil (5-FU, 700 mg/m2/d) and folinic acid (FA, 300 mg/m2/d) combined with oxaliplatin (l-OHP, a nonnephrotoxic platinum complex, 25 mg/m2/d) were infused continuously for 5 days every 3 weeks. In a pilot randomized study, the infusion of all three drugs at a constant rate resulted in World Health Organization (WHO) Grade 3 or 4 toxicity in all four patients compared with no such toxicity in four patients if the infusion rate was modulated according to circadian rhythms. In this Phase II trial, drug delivery was modulated sinusoidally over the 24-hour day with peak flow rates at 4 AM for 5-FU and FA and at 4 PM for l-OHP, using an ambulatory programmable-in-time pump. All patients and 784 of 839 courses (93%) were evaluable for toxicity. Dose-limiting toxicities (WHO Grade 2 to 4) included diarrhea (19% of courses) and vomiting (35% of courses). In addition, WHO Grade 2 to 4 hematologic or mucosal toxicity, respectively, occurred in 2.5% and 7% of courses. Two toxic deaths were encountered. Peripheral sensory neuropathy led to discontinuation of l-OHP in 14 patients after 7 to 12 courses; it completely disappeared within 3 months. Fifty-four of the 93 patients had an objective response (58%; 95% confidence limits, 48% to 68%), irrespective of previous treatment or prior documented progression while receiving standard chemotherapy with 5-FU and FA or continuous 5-FU. Complete responses (CR) were seen in 6 patients (4 of which were proved histologically) and, after surgery, in 12 additional patients (overall CR rate, 18 of 93 [19%]; 95% confidence limits, 11% to 27%). Median progression-free survival (PFS) and overall survival were, respectively, 10 and 15 months, irrespective of prior therapy. Both PFS and survival were significantly longer in patients with a good performance status (PS, 0 or 1, by WHO criteria; respectively, 12 and 21 months) than in patients with poor PS (respectively, 8 and 10 months; P less than 0.01, by log-rank test). This chronopharmacologic protocol may have circumvented, to some extent, both the natural and acquired resistance of colorectal cancer to chemotherapy.

[What is the method of choice for hemodynamic monitoring in liver transplantation?]. / Quel monitorage hémodynamique lors des transplantations hépatiques?

Orthotopic liver transplantation requires close hemodynamic monitoring. Technological advances provide new possibilities of improving this monitoring. The most recent devices are the mixed venous oxygen saturation catheter, which gives continuous SVO2 values, and the right ejection fraction catheter used discontinuously. Our experience of 100 liver transplantations has enabled us to investigate the advantages of these catheters over the conventional Swan Ganz catheters.

Phase I-II constant infusion of adriamycin (doxorubicin) by ambulatory pump delivery system in heavily pretreated (including adriamycin) breast cancer patients.

Previous studies have shown that the protracted infusion of adriamycin (ADM) by the ambulatory delivery system can significantly decrease both the cardiac and hematological toxicity caused by intermittent bolus administration. We treated 27 patients with metastatic breast cancer who had been heavily pretreated with regimens including ADM. Treatment consisted of 15- or 25-day courses of ADM at a mean dose of 3.8 mg/m2 (2.2-4.5 mg/m2) infused by programmable portable pump. Early cardiac toxicity was detected by echocardiography-Doppler. Two-dimensional echocardiography made possible the detection of interventricular septum hypokinetics, an early sign of a decrease of systolic function of the left ventricle. Despite the very high cumulative dose of ADM (mean dose 777.79 mg/m2, range 282-1647 mg/m2) received by these patients, no clinical heart failure was observed. Most frequently observed complications were oral mucositis, Grade 2 and 3 (10 patients), and complications related to the drug delivery system (15/137 courses). Hematological toxicity was minimal. Seven Grade 2 and five Grade 3 (but no Grade 4) alopecia were observed. Objective response was obtained in four of 24 patients (17%) evaluated for response, (only 21 were fully evaluable): one complete response and three partial responses (duration: 6.6, 7 and 11 months, respectively). Stabilization was seen in 14 patients lasting three to 26 months. The performance status and symptoms of nine of the patients (37%) was significantly improved. Our results show that continuous infusion of ADM is well tolerated and provides palliation to patients with metastatic breast cancer. It merits a trial as first-line treatment.

Emergency orthotopic liver transplantation in two patients using one donor liver.

Because of its anatomy, the liver can be divided into two hemilivers suitable for use as two grafts for liver transplantation. The line of division is the main scissure, giving the right hemiliver (segments 5-8) and the left hemiliver (segments 2-4). Segment 1 (caudate lobe) has to be resected. The vessels are divided between the two grafts: the vena cava remains on the right; on the left, the left hepatic vein is sutured into the vena cava of the recipient, which is retained intact. The left graft retains only the left branch of the portal vein, the bile duct and the hepatic artery. The right graft retains the portal trunk, the common bile duct and the right branch of the hepatic artery. This procedure was used for emergency grafting of two patients with fulminant hepatitis when only one donor was available. Both recipients recovered from coma and regained normal liver function. However, both died from causes not specifically related to the operative technique, one from multiple organ failure on the 20th day and the other from diffuse cytomegalovirus infection on the 45th day.