6% Hydroxyethyl starch (130/0.4) vs Ringer's lactate preloading before spinal anaesthesia for Caesarean delivery: the randomized, double-blind, multicentre CAESAR trial.

BACKGROUND: Vasopressor administration is recommended to prevent hypotension during spinal anaesthesia (SA) for elective Caesarean delivery. We aimed to test the superior efficacy and ensure safety of a hydroxyethyl starch (HES) vs a Ringer's lactate (RL) preloading, when combined with a phenylephrine-based prophylaxis. METHODS: A total of 167 healthy parturients undergoing elective Caesarean delivery under SA were included in this multicentre, randomized, double-blind study. Patients received 500 ml of 6% HES (130/0.4)+500 ml of RL (HES group) or 1000 ml of RL (RL group) i.v. before SA. After SA, i.v. phenylephrine boluses were titrated when systolic arterial pressure (SAP) was below 95% of baseline. The primary outcome was the incidence of maternal hypotension (SAP <80% of baseline). RESULTS: The incidence of both hypotension and symptomatic hypotension (i.e. with dizziness, nausea/vomiting, or both) was significantly lower in the HES group vs the RL group: 36.6% vs 55.3% (one-sided P=0.025) and 3.7% vs 14.1%. There was no significant difference in total phenylephrine requirements [median (range): 350 (50-1800) vs 350 (50-1250) µg]. The decrease in maternal haemoglobin value the day after surgery was similar in the two groups [1.2 (1.0) vs 1.0 (0.9) g dl(-1)]. There was no detectable placental transfer of HES in six umbilical cord blood samples analysed in the HES group. Neonatal outcomes were comparable between the groups. CONCLUSIONS: Compared with a pure RL preloading, a mixed HES-RL preloading significantly improved prevention of both hypotension and symptomatic hypotension based on early phenylephrine bolus administration and did not induce adverse effects. CLINICAL TRIAL REGISTRATION: NCT00694343 (http://clinicaltrials.gov).

Seizures in the peripartum period: Epidemiology, diagnosis and management.

The occurrence of seizures in the peripartum period is a rare but particularly challenging situation. Seizures in the peripartum period could result from three categories of conditions: first and most frequent is the exacerbation of a known pre-existing seizure disorder, mainly epilepsy. A therapeutic evaluation is needed; second is the new onset of seizures due to a non-pregnancy-related problem. An accurate diagnosis and a specific treatment are required; third is range of pregnancy-related conditions. The present review focuses on this third category, with a special attention to disorders occurring in the peripartum period. It is structured in two sections. The first section is a focus on eclampsia since, based on ICU admission data, it appears to be the leading cause of pregnancy-related seizures. Its epidemiology, pathophysiology, clinical diagnosis, neuro-imaging features and recommended management are reviewed. The efficacy and safety of the recommended regimens of MgSO4 therapy are discussed, as well as controversies on the alteration of these regimens and the use of MgSO4 in women with mild preeclampsia. In the second section, the other causes of pregnancy-related new onset seizures are summarized. These include posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, cerebral venous sinus thrombosis, thrombotic thrombocytopenic purpura, amniotic fluid embolism, and air embolism. Noteworthy is the fact that most of these pregnancy-related seizure conditions overlap with each other, mainly in terms of clinical presentations and neuro-imaging. Therefore, the diagnosis and the treatment options should be considered on a multidisciplinary basis.

Recombinant human FVIIa for reducing the need for invasive second-line therapies in severe refractory postpartum hemorrhage: a multicenter, randomized, open controlled trial.

BACKGROUND: Case reports on recombinant human factor VIIa (rhuFVIIa) use in women with severe postpartum hemorrhage (PPH) showed encouraging results, but no randomized controlled trial (RCT) is available. PATIENTS AND METHODS: Eighty-four women with severe PPH unresponsive to uterotonics were randomized to receive one early single rhuFVIIa infusion (n = 42) or standard care (no rhuFVIIa; n = 42). The primary efficacy outcome measure was the reduction of the need for specific second-line therapies, such as interventional hemostatic procedures, for blood loss and transfusions. The primary safety outcome measure was the number of deaths and thrombotic events during the 5 days following rhuFVIIa infusion. RESULTS: rhuFVIIa was associated with a reduction in the number of patients who needed second-line therapies compared with controls (standard care). Specifically, 39/42 (93%) patients in the standard care arm received second-line therapies and 22/42 (52%) patients in the rhuFVIIa arm (absolute difference, 41%; range, 18-63%; relative risk RR, 0.56 [0.42-0.76]). The delivery mode (vaginal or Cesarean section) did not affect the primary outcome. No death occurred. Two venous thrombotic events were recorded in the rhuFVIIa arm: one ovarian vein thrombosis and one deep vein thrombosis with a non-severe pulmonary embolism. CONCLUSION: This open RCT in women with severe PPH refractory to uterotonics shows that rhuFVIIa reduces the need for specific second-line therapies in about one in three patients, with the occurrence of non-fatal venous thrombotic events in one in 20 patients.

Intravenous nicardipine for severe hypertension in pre-eclampsia--effects of an acute treatment on mother and foetus.

OBJECTIVES: To assess the efficacy in lowering blood pressure, and the safety for mother and foetus of an acute nicardipine therapy in severe pre-eclampsia. DESIGN: Prospective clinical study. SETTING: One university hospital obstetric unit. PATIENTS: Twenty consecutive adult pre-eclamptic patients with severe hypertension. INTERVENTION: Nicardipine, 1 microgram/kg per min, was given intravenously to lower the mean arterial pressure (MAP) by at least 15%. Then, the dosage was reduced by 1/3, and the final dosage was determined to maintain MAP at 20-30% below the initial value, by increasing or decreasing the infusion rate by 0.5 mg/h. MEASUREMENTS AND RESULTS: Maternal MAP and heart rate (HR) were assessed every 5 min for 1 h. Foetal HR (FHR) was recorded throughout the study period and assessed for Fischer score. Gestational age, Apgar scores, birth weight, capillary filling time and the duration of stay in the paediatric intensive care unit (ICU) were used to evaluate the short-term perinatal outcome. A 15-30% decrease in MAP occurred within 15-20 min in all patients. An increase in HR was noted, and two patients had severe tachycardia. Maternal side effects included flushing, headache, nausea and dizziness. FHR showed a transient decrease in acceleration episodes and occurrence of decelerations. No nicardipine-related foetal distress occurred. Four infants born during the study period did well at birth and had a good outcome. CONCLUSIONS: Acute nicardipine therapy can induce severe maternal tachycardia. No severe foetal or neonatal adverse effects occurred. This dose scheme requires comparison with alternative therapeutic options.

CO assessment by suprasternal Doppler in critically ill patients: comparison with thermodilution.

OBJECTIVE: Comparison of suprasternal Doppler (SST) and thermodilution (TD) for the measurement of cardiac output (CO) in critically ill patients. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: 65 consecutive critically ill patients requiring a pulmonary artery catheter. INTERVENTIONS: Paired CO measurements were made simultaneously using SST and TD by two independent operators. The time to obtain a CO value by SST was measured. Correlation coefficients and the linear regression equation were determined. A Bland and Altman diagram was plotted. A Bland and Altman diagram was also plotted for the level of cardiac index (CI) values (low: CI < 2.5 l min(-1) m(-2); normal: 2.5 < or = CI < or = 4.5 l min(-1) m(-2); high: CI > 4.5 l min(-1) m(-2)). MEASUREMENTS AND RESULTS: In seven patients SST failed to measure CO. In the remaining 58 patients 314 paired CO measurements were performed. The mean time to measure CO by SST was 73 +/- 45 s. The equation of linear regression was: SST(CO) = 0.84 TD(CO) + 1.39. The correlation coefficient was 0.84. The bias between SST and TD was -0.2 +/- 1.4 l min(-1). Biases were -0.23 +/- 0.50, -0.20 +/- 0.68, and 0.25 +/- 0.92 l min(-1) m(-2) for low, normal, and high levels of CI, respectively. CONCLUSION: SST does not accurately measure CO but allows a rapid assessment of CI level in critically ill patients.

Training is required to improve the reliability of esophageal Doppler to measure cardiac output in critically ill patients.

OBJECTIVES: Assessment of and effect of training on reliability of esophageal Doppler (ED) versus thermodilution (TD) for cardiac output (CO) measurement. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS: 64 consecutive critically ill patients requiring a pulmonary artery catheter, sedation, and mechanical ventilation. INTERVENTIONS: Esophageal Doppler CO measurements were performed by the same operator, whereas TD CO measurements were carried out by other independent operators. A training period involving the first 12 patients made the operator self-confident. In the remaining patients, the reliability of ED was assessed (evaluation period), using correlation coefficients and the Bland and Altman diagram. Between training and evaluation periods, correlation coefficients, biases, and limits of agreement were compared. MEASUREMENTS AND RESULTS: During training and evaluation periods, 107 and 320 CO measurements were performed in 11 out of 12 patients and in 49 out of 52 patients, respectively. Continuous CO monitoring was achieved in 6 out of 11 patients and in 38 out of 49 patients during training and evaluation periods, respectively. Between the two periods, correlation coefficients increased from 0.53 to 0.89 (p < 0.001), bias decreased from 1.2 to 0.1 l x min(-1) (p < 0.001), and limits of agreement decreased from 3.2 to 2.2 l x min(-1) (p < 0.001). CONCLUSION: A period of training involving no more than 12 patients is probably required to ensure reliability of CO measurement by ED.

[Severe preeclampsia. Principal management modalities before patient transfer]. / Pré-éclampsie sévère. Principales modalités de la prise en charge avant transfert.

Preeclampsia is relatively frequent during pregnancy. The occurrence of complications implies referral to a specialized center for optimal care of both mother and fetus. The transfer of these patients is very critical with risk of worsening the mother's status. Management before referral aims to stabilize material clinical status, requiring precise clinical assessment, treatment of severe hypertension or pulmonary edema, and prevention or treatment of eclampsia. The management of oliguria and the tracheal intubation are associated with specific problems. Fetal wellbeing is assessed before and during emergency treatments of maternal disorders.

[Severe preeclampsia. Analysis of a case with fatal outcome]. / Pré-éclampsie sévère. Analyse d'un cas d'évolution fatale.

We report a case of preeclampsia presenting initially as a moderate hypertension, and complicated over a ten-day period by eclampsia, retinal hemorrhage, cerebral and hepatic subcapsular hematomas, HELLP syndrome, disseminated intravascular coagulation and renal failure. Fatal outcome was related to cerebral death and rupture of the liver hematoma. The case analysis points out inaccurate initial management: probable misdiagnosis of epigastric pain related to subcapsular hematoma, ineffective antihypertensive therapy, aspiration of the gastric content after benzodiazepine treatment of eclampsia, transfer of the patient without stabilisation of her clinical status.

[Dural puncture in obstetric analgesia. Epidemiologic features and therapeutic management]. / Brèche durale en analgésie obstétricale. Aspects épidémiologiques et prise en charge thérapeutique.

OBJECTIVE: To assess the time of occurrence, circumstances and presenting symptoms of unintentional dural puncture (UDP), the location and intensity of postdural puncture headaches (PDPH), and the efficacy of their treatment by epidural blood-patch (EBP). STUDY DESIGN: Cohort study. PATIENTS: Cases of UDP recorded over a 4-year period in an obstetric anaesthesia unit. METHODS: The following variables were studied: maternal age, weight and height, hour of occurrence and number of puncture attempts, existence of reflux of cerebrospinal fluid (CSF) through the needle, experience of the practitioners, subsequent modalities of obstetrical analgesia, frequency of occurrence, clinical characteristics and therapeutic management of PDPH. In case of EBP, the amount of blood and the efficacy of the procedure were also recorded. RESULTS: Twenty-one patients presented with UDP (0.66%). No reflux of CSF was identified in nine cases. Most UDP occurred at the first or second attempt, usually when performed by a practitioner poorly trained in epidural analgesia in obstetrics. The risk of UDP was higher during night-time work (risk ratio: 3.0; 95% confidence interval: 1.1-8.0; p = 0.04). Subsequent analgesia was provided via the epidural route in 19 cases, subarachnoidal route in one, and intravenous route in one case. PDPH did not develop in two patients. Three patients were given prophylactic EPB, and 16 received curative EBP. A second EBP was required 24 h later in seven patients. One patient developed meralgia paresthetica following EBP. CONCLUSION: In parturients, UDP usually results in PDPH. A rapid and effective treatment is required, mainly EBP. Another EBP is eventually necessary in some patients.

[Anesthetic management of severe or worsening postpartum hemorrhage]. / Prise en charge anesthésique d'une hémorragie du post-partum sévère ou résistant au traitement médical.

INTRODUCTION: Risk factors of maternal morbidity and mortality during postpartum hemorrhage (PPH) include non-optimal anesthetic management. As the anesthetic management of the initial phase is addressed elsewhere, the current chapter is dedicated to the management of severe PPH. METHODS: A literature search was performed using PubMed and Medline databases, and the Cochrane Library, for articles published from 2003 up to and including 2013. Several keywords related to anesthetic and critical care practice, and obstetrical management were used, in various combinations. Guidelines from several societies and organisations were also read. RESULTS: When PPH worsens, one should ask for additional team personnel (professional consensus). Patients should be monitored for heart rate, blood pressure, skin and mucosal pallor, bleeding at skin puncture sites, diuresis and the volume of genital bleeding (grade B). Because of the possible rapid worsening of coagulapathy, patients should undergo regular evaluation of coagulation status (professional consensus). Prevention and management of hypothermia should be considered (professional consensus), by warming intravenous fluids and blood products, and by active body warming (grade C). Antibiotics should be given, if not already administered at the initial phase (professional consensus). Vascular fluids must be given (grade B), the choice being left at the physician discretion. Blood products transfusion should be decided based on the clinical severity of PPH (professional consensus). Priority is given to red blood cells (RBC) transfusion, with the aim to maintain Hb concentration>8g/dL. The first round of products could include 3 units of RBC (professional consensus), and the following round 3 units of RBC, and 3 units of fresh frozen plasma (FFP). The FFP:RBC ratio should be kept between 1:2 and 1:1 (professional consensus). Depending on the etiology of PPH, the early administration of FFP is left at the discretion of the physician (professional consensus). Platelet count should be maintained at>50 G/L (professional consensus). During massive PPH, fibrinogen concentration should be maintained at>2g/L (professional consensus). Fibrinogen can be given without prior fibrinogen measurement in case of massive bleeding (professional consensus). General anesthesia should be considered in case of hemodynamic instability, even when an epidural catheter is in place (professional consensus). CONCLUSION: The anesthetic management aims to restore and maintain optimal respiratory state and circulation, to treat coagulation disorders, and to allow invasive obstetrical and radiologic procedures. Clinical and instrumental monitoring are needed to evaluate the severity of PPH, to guide the choice of therapeutic options, and to assess treatments efficacy.

[Anesthesia and preeclampsia]. / Anesthésie et prééclampsie.

An assessment of the patient must take place as early as possible in view of anaesthesia. It is recommended to perform a clotting screen as close as possible to the performing of an epidural anaesthesia. The use of aspirin, if indicated for the prevention of PE, does not as such, constitute a contraindication to performing an epidural anaesthesia if: With regards to the minimum platelet count, the recommended cut-off value for the performing of an epidural and spinal anaesthesia are 75 & 50 x 10(9)/l respectively, only if all of the following conditions are met: It is recommended to quickly set up an epidural anaesthesia because this will improve the blood pressure as well as the utero-placenteric haemodynamics and also because this will facilitate the management in case of a caesarean section. Whereas methylergometrine (Methergin) is contraindicated in the preeclamptic patient, it is possible to use oxytocin (Syntocinion) during and after labour. Before performing a spinal anaesthesia, it is recommended to restrain the administration of crystalloids to a maximum of 1000 ml. Also the i.v. antihypertensive treatment should be reduced or interrupted until complete establishment of the anaesthetic. In case a general anaesthesia is to be performed, an assessment of the criteria for difficult intubation should be performed immediately prior to the induction. The technique employed should be a rapid sequence induction with intubation, while preventing a surge in blood pressure induced by the tracheal intubation. Difficulties to extubate should systematically be anticipated. It is possible to perform a loco-regional anaesthesia following an eclamptic crisis if the following conditions are met: In case of overlapping seizures and/or impaired consciousness, a general anaesthesia is recommended.

[Lipid emulsions for the treatment of systemic local anesthetic toxicity: Efficacy and limits]. / Les émulsions lipidiques dans le traitement de la toxicité systémique des anesthésiques locaux : efficacité et limites.

Local anaesthetic toxicity always results from rapid and important increase in their plasma concentrations. Clinically, neurologic and cardiovascular symptoms may occur, especially life-threatening cardiac arrhythmias and cardiac depression. Resuscitating patients from cardiac toxicity was known as difficult, until the introduction of lipid emulsion therapy. From experimental data, at least two mechanisms of action can be proposed, a sink-effect and an improvement of cardiomyocyte metabolism. The present article is a mini-review of the current use of lipid emulsions for the treatment of local anaesthetic cardiac toxicity. The mechanisms of cardiac toxicity and those of lipid emulsion therapy are summarized, and the clinical experience of this therapy and its limits are presented.

Increased risk of unintentional dural puncture in night-time obstetric epidural anesthesia.

PURPOSE: To evaluate the experience of the operator and the time of epidural anesthesia as factors contributing to unintentional dural puncture (UDP). METHODS: In a prospective analysis of recorded cases of UDP the following variables were recorded: maternal height, weight, and weight gain, type of personnel providing epidural analgesia, number of attempts, and hour of the epidural procedure. Work time was divided into day-time (8 AM to 7 PM) and night-time (7 PM to 8 AM), according to the change of coverage of the delivery suite. Night-time was divided into first (7 PM to midnight) and second parts (midnight to 8 AM). Relative risk was used to compare the incidence of UDP among different work-times. RESULTS: A total of 1489 consecutive epidural procedures were considered. The incidence of dural puncture was 0.8% (12 cases). The relative risk was higher for night-time than day-time (risk ratio 6.33; 95% confidence interval, 1.39 to 28.80; P = 0.006). Seven cases were caused by three operators with poor expertise, and five by two skilled obstetric anesthesiologists. CONCLUSION: Operator experience and hour of procedure appear to be two important risk factors of UDP The increased risk of UDP in night-work could result from human factors such as fatigue, sleep deprivation or interruption.

Severe preeclampsia superimposed on polyarteritis nodosa.

A patient with a history of drug abuse and histologically diagnosed hepatitis B-related polyarteritis nodosa was admitted for severe hypertension. After a cesarean section because of worsening of her clinical status with severe proteinuria and edema, she improved dramatically. No sign of acute polyarteritis nodosa occurred.

Mechanisms of ventricular arrhythmias induced by myocardial contusion: a high-resolution mapping study in left ventricular rabbit heart.

BACKGROUND: The aims of the Langendorff-perfused rabbit heart study were to evaluate the arrhythmogenic consequences of myocardial contusion and to determine the mechanism of arrhythmia. METHODS: Six hearts were in the control group, and 24 hearts (intact heart protocol) were submitted to one of four different contusion kinetic energies (75, 100, 150, or 200 millijoules [mJ]; n = 6). Occurrence of arrhythmia, of an electrically silent area (i.e., area with no electrical activity), and of line of fixed conduction block were reported before and for 1 h after contusion. In 16 hearts (frozen hearts) submitted to cryoprocedure and contusion impact of 100 or 200 mJ, ventricular conduction velocities, anisotropic ratio, wavelengths, ventricular effective refractory period, and its dispersion were measured before and for 1 h after contusion. Using high-resolution mapping, arrhythmias were recorded and analyzed. RESULTS: The intact heart study showed that the number and seriousness of contusion-induced arrhythmias increased with increasing contusion kinetic energy, as did the number of electrically silent areas (five of six ventricular fibrillations and five of six electrically silent areas at 200 mJ). In the frozen heart study, immediately after contusion ventricular effective refractory periods were shortened and dispersed, and wavelengths were also shortened. The arrhythmia analysis showed that all ventricular tachycardias but one were based on reentry developed around an electrically silent area or a line of fixed conduction block. CONCLUSIONS: Myocardial contusion has direct arrhythmogenic effects, and the seriousness of arrhythmia increases with the level of contusion kinetic energy. The mechanism of arrhythmia was mainly based on reentrant circuit around a fixed obstacle.

Chronobiology of labour pain perception: an observational study.

BACKGROUND: Circadian variation may affect many biological and pharmacological phenomena. METHODS: To assess circadian variations in labour pain perception, 222 consecutive nulliparous women with uncomplicated pregnancy, spontaneous labour, cervical dilatation (3-5 cm), ruptured membranes and normal fetal heart rate tracings were studied. Visual analogue pain scores (VAPS) were analysed and divided into four periods: night (1:01 a.m. to 7:00 a.m.), morning (7:01 a.m. to 1:00 p.m.), afternoon (1:01 p.m. to 7:00 p.m.) and evening (7:01 p.m. to 1:00 a.m.). VAPS were also compared between daytime (morning+afternoon) and nocturnal (evening+night) periods. RESULTS: Daytime mean VAPS were lower than nocturnal scores [75.6 (15.1) vs 85.7 (14.1), P<0.0001]. VAPS were lower in the morning than in the afternoon, evening and night periods (anova, P<0.0001). CONCLUSION: Labour pain perception appears to be chronobiological, and this might be taken into account when enrolling parturients in studies designed to assess or treat labour pain.

Dispersion-based reentry: mechanism of initiation of ventricular tachycardia in isolated rabbit hearts.

The aim of the study was to determine whether facilitation of reentry by potassium-channel openers is related to dispersion of refractoriness and/or modification of anisotropic properties of ventricular myocardium. The dispersion of ventricular effective refractory period (VERP), longitudinal and transverse ventricular conduction velocities (thetaL and thetaT, respectively), and wavelength [lambda = VERP x theta(L or T)] were studied in Langendorff-perfused left ventricular epicardium in 20 rabbits during infusion of incremental doses of levcromakalim or nicorandil. Dispersion of refractoriness was assessed using standard deviation of VERP mean (SD-VERP), dispersion index (DI; SD-VERP/mean VERP), and maximum dispersion (Dmax = VERPmax - VERPmin). Ventricular conduction velocities and anisotropic ratio were not modified, whatever the dose used. VERP and lambda were significantly shortened at high concentrations of levcromakalim and nicorandil. At these doses, SD-VERP, DI, and Dmax were increased significantly. Analysis of ventricular tachycardia induction, performed using a high-resolution ventricular mapping system, confirmed that heterogeneity and shortening of VERP were factors inducing functional conduction block. Our data suggest that, in rabbit left ventricular epicardium, functional conduction block facilitating the occurrence of reentry could be initiated by shortening and, especially, by dispersion of refractoriness during infusion of potassium-channel openers.