Marc Van de Velde

Long-chain triglycerides improve recovery from myocardial stunning in conscious dogs.

OBJECTIVES Free fatty acid (FFA) oxidation is depressed in the postischaemic stunned myocardium and recovers in parallel with the normalization of contractile performance. Assuming a causal role for this metabolic disturbance in the pathogenesis of stunning, we questioned whether exogenous administration of high dose triglycerides during reperfusion of postischaemic myocardium, could improve its functional recovery. METHODS Thirteen dogs were chronically instrumented to measure global and regional haemodynamics and to produce a 10 min episode of regional myocardial ischaemia. In 7 dogs, Intralipid 20% was administered i.v. during the reperfusion phase. Contractile recovery of stunned myocardium was compared with control saline treatments. The series were repeated in another 6 animals, but oxfenicine (CPT I inhibitor) preceeded Intralipid during reperfusion. RESULTS Contractile recovery of stunned myocardium was faster and more extensive when Intralipid was administered during reperfusion than with saline treatment (wall thickening fraction 86 +/- 6% of preischaemic controls versus 52 +/- 11% at 90 min post-reperfusion; P < 0.05). Oxfenicine pretreatment completely abolished this beneficial effect. CONCLUSIONS Exogenous administration of triglycerides during reperfusion of postischaemic myocardium improves functional recovery from stunning. This beneficial effect most likely operates through enhanced FFA availability and/or oxidation since it could be abolished by selective inhibition of the carnitine palmitoyl I enzyme.

Major Obstetric Hemorrhage

Major obstetric hemorrhage remains the leading cause of maternal mortality and morbidity worldwide, and is associated with a high rate of substandard care. A well-defined and multidisciplinary approach that aims to act quickly and avoid omissions or conflicting strategies is key. The most common etiologies of hemorrhage are abruptio placenta, placenta previa/accreta, uterine rupture in the antepartum period and retained placenta, uterine atony, and genital-tract trauma in the postpartum period. Basic treatment of postpartum hemorrhage relies on manual removal of the placenta or manual exploration of the uterus plus bladder emptying and oxytocin administration. If this does not arrest bleeding, or if there is any suspicion of genital-tract trauma, examination of the vagina and cervix with appropriate valves and analgesia/anesthesia must follow quickly. Postpartum uterine atony resistant to oxytocin must be treated with prostaglandin within 15 to 30 minutes; uterine balloon tamponade can be also useful at this stage. Aggressive transfusion therapy and resuscitation are mandatory in major obstetric hemorrhage. Specific invasive treatment must be considered within no more than 30 to 60 minutes, if previous measures have failed -- and even earlier in some particular etiologies. The two main options are radiologic embolization and surgical artery ligations. Recombinant factor VIIa may also be considered, but should not delay the performance of a life-saving procedure such as embolization or surgery. Hysterectomy must be implemented when all other interventions have failed.

Low-dose spinal anaesthesia for Caesarean section to prevent spinal-induced hypotension.

Purpose of review The present review evaluates the evidence available in the literature to see whether low-dose spinal anaesthesia for Caesarean section is effective in preventing maternal hypotension while at the same time guaranteeing effective anaesthetic conditions. Main findings From prospective trials, it is clear that lowering the spinal dose improves maternal haemodynamic stability. Doses of intrathecal bupivacaine between 5 and 7 mg are sufficient to provide effective anaesthesia. Complete motor block is, however, seldom achieved and adequate anaesthesia is limited in time. Summary Low-dose spinal anaesthesia as part of a combined spinal–epidural technique is a valuable method in improving maternal and fetal outcome during anaesthesia for operative delivery.

Determination of the Full Dose–response Relation of Intrathecal Bupivacaine, Levobupivacaine, and Ropivacaine, Combined with Sufentanil, for Labor Analgesia

Background:Ropivacaine and levobupivacaine are local anesthetics that produce less motor block and greater sensory–motor separation when compared with equal milligram doses of bupivacaine. Although minimum local analgesic concentration studies suggested that they are less potent than bupivacaine, full dose–response studies have not been performed. The current trial describes the dose–response relation of levobupivacaine, ropivacaine, and bupivacaine, combined with sufentanil, when used for intrathecal labor analgesia. Methods:Four hundred fifty term parturients in active labor were included in this double-blind, randomized trial. Combined spinal–epidural anesthesia was performed, and ropivacaine, levobupivacaine, or bupivacaine was intrathecally administered in a dose of 1.0, 1.5, 2.0, 2.5, 3.0, or 3.5 mg, always combined with 1.5 &mgr;g sufentanil. Patients were considered responders to spinal analgesia if the visual analog scale score for pain was less than 25 mm within 15 min and the visual analog scale score remained less than 25 mm for 45 min. Patient demographics, obstetric data, maternal side effects, and fetal and neonatal well-being were noted. Group-specific dose–response curves were constructed using a probit regression model. Results:The ED95 of bupivacaine was 3.3 mg (95% confidence interval, 2.9–4.1). The ED95s of ropivacaine and levobupivacaine were 4.8 mg (95% confidence interval, 4.0–6.7) and 5.0 mg (95% confidence interval, 4.1–7.0), respectively. Racemic bupivacaine was significantly more potent than ropivacaine (P = 0.0027) and levobupivacaine (P = 0.0006). Ropivacaine and levobupivacaine were of similar potency (P = 0.91). Conclusions:This full dose–response study suggests that ropivacaine and levobupivacaine are of similar potency, whereas bupivacaine is more potent than both other drugs.

Hemodynamic changes during induction of anesthesia with eltanolone and propofol in dogs

The purpose of this study was to examine global and regional hemodynamic changes during induction of anesthesia with eltanolone, a new short-acting steroid hypnotic, as compared to propofol, in chronically instrumented dogs. The effects on cardiac performance were assessed in six animals. Renal and hepatic blood flows were examined in a separate study including five animals. Two doses of each drug were investigated: eltanolone 2.5 and 5 mg/kg and propofol 7.5 and 15 mg/kg. Left atrial filling pressures and cardiac output were not affected by either drug. Maximum rate of increase of left ventricular pressure decreased both with eltanolone (-28% and -40% from awake control for the 2.5 and 5 mg/kg doses, respectively) and with propofol (-19% and -30% from awake controls with 7.5 and 15 mg/kg, respectively). In contrast to propofol, eltanolone preserved arterial blood pressure. Propofol lowered systemic vascular resistance (-21% and -39% with the low and high dose, respectively), and only slightly decreased left ventricular wall thickening fraction (-16% and -21%). Eltanolone did not affect systemic vascular resistance but reduced the wall-thickening fraction dose-dependently (-28% and -61%). Propofol, but not eltanolone, induced moderate coronary vasodilation. Hepatic arterial blood flow velocity decreased dose-dependently (-21% and -64%) during eltanolone anesthesia whereas, in contrast, it increased after propofol (+59% and +64%). Renal and portal venous blood flows remained essentially unaltered from awake conditions. Our data demonstrate that both propofol and eltanolone have cardiodepressant properties but differ with regard to their effects on peripheral vascular tone. Systemic arterial vasodilation, as caused by propofol, may prove more favorable to overall cardiac performance. Liver blood flow was also better preserved with propofol when compared to eltanolone. (Anesth Analg 1995;81:125-31)

Effects of lipids on the functional and metabolic recovery from global myocardial stunning in isolated rabbit hearts

OBJECTIVES High concentrations of free fatty acids may increase myocardial ischaemic damage. However, the administration of lipid emulsions during reperfusion improves the functional recovery of stunned myocardium. From this apparent controversy we hypothesise that the effect of lipids is related to the time of its administration: we compared the effects of pre- and post-ischaemic administration of Intralipid((R)) on stunned myocardium. We also examined the role of fatty acids and phospholipids, respectively, in the effect of lipid emulsions on stunned myocardium. METHODS Myocardial stunning was produced by 15 min of ischaemia and 90 min of reperfusion in isolated blood perfused rabbit hearts. Intralipid((R)) was administered either prior to ischaemia or during reperfusion. Left ventricular pressure (LVP) and its first derivative (LVdP/dt) were measured to assess functional recovery. High energy phosphates were measured with HPLC. The effects of linoleic acid, phosphatidylcholine and their combination were also studied. RESULTS Only when Intralipid((R)) was administered during reperfusion, it improved recovery from contractile function and increased high energy phosphate content in globally stunned myocardium. Both linoleic acid and phosphatidylcholine significantly improved myocardial function in stunned myocardium. CONCLUSIONS The effect of lipids on the contractile performance and metabolic state of stunned myocardium depends mainly on the timing of its administration with regard to the ischaemia/reperfusion event. Both free fatty acids and phospholipids contribute to the beneficial effect of lipid emulsions on functional recovery of stunned myocardium.

Combined spinal-epidural anesthesia for cesarean delivery: dose-dependent effects of hyperbaric bupivacaine on maternal hemodynamics.

Hypotension remains an important side effect of spinal anesthesia for cesarean delivery. There is limited evidence that reducing the spinal dose has a favorable effect on maternal hemodynamic stability. We designed the present randomized trial to test the hypothesis that reducing the spinal dose of local anesthetics results in equally effective anesthesia and less maternal hypotension. Fifty term pregnant patients were randomly assigned to two study groups. In the HIGH-group combined spinal-epidural anesthesia was performed using 9.5 mg hyperbaric bupivacaine combined with 2.5 &mgr;g sufentanil. In the LOW-group combined spinal-epidural anesthesia was performed using 6.5 mg hyperbaric bupivacaine combined with 2.5 &mgr;g sufentanil. Demographic data, obstetrical data, visual analog scale score for pain, number of medical interventions for pain, maternal hemodynamics, and neonatal outcome were recorded. Patients in the HIGH-group experienced more pronounced and longer hypotensive periods as compared with the LOW-group. The mean lowest recorded systolic blood pressure was higher in the LOW-group (102 ± 16 versus 88 ± 16 in the HIGH-group; P < 0.05). More patients in the HIGH-group experienced hypotension compared with the LOW-group (68% versus 16%; P < 0.05). In the HIGH-group 15 patients required pharmacological treatment for hypotension compared with 5 in the LOW-group. Duration of effective anesthesia (block to cold sensation above or at T3) was longer in the HIGH-group as compared with the LOW-group (95 ± 25 versus 68 ± 18 min, respectively, P < 0.05). We conclude that small-dose spinal anesthesia (6.5 mg hyperbaric bupivacaine combined with sufentanil) better preserves maternal hemodynamic stability with equally effective anesthesia that is of shorter duration.

Remifentanil for fetal immobilization and maternal sedation during fetoscopic surgery: a randomized, double-blind comparison with diazepam.

Obstetric endoscopy procedures are routinely performed at our institution to treat selected complications of monochorionic twin gestation. We perform these procedures under combined spinal epidural anesthesia plus maternal sedation. In the absence of general anesthesia, fetal immobilization is not achieved. We hypothesized that remifentanil would induce adequate maternal sedation and provide fetal immobilization, which is equal or superior to that induced by diazepam. Fifty-four second trimester pregnant women were included in this randomized, double-blind trial. After combined spinal epidural anesthesia, maternal sedation was initiated using either incremental doses of diazepam or a continuous infusion of remifentanil. Maternal sedation, hemodynamics, side effects, and fetal hemodynamics and immobilization were evaluated before, during, and for 60 min after surgery. Remifentanil produced adequate maternal sedation with mild but clinically irrelevant respiratory depression (respiratory rate 13 ± 4 breaths/min and Pco2 38.6 ± 4 mm Hg at 40 min of surgery), whereas diazepam resulted in a more pronounced maternal sedation but no respiratory depression (respiratory rate 18 ± 3 breaths/min and Pco2 32.7 ± 3 mm Hg at 40 min of surgery). Compared with diazepam, fetal immobilization with remifentanil occurred faster and was more pronounced, resulting in improved surgical conditions; the number of gross body and limb movements was 12 ± 4 (diazepam) versus 2 ± 1 (remifentanil) at 40 min of surgery. Because of this, the mean (range) duration of surgery was significantly shorter in the remifentanil-treated patients, 60 (54–71) min versus 80 (60–90) min in the diazepam group. We conclude that remifentanil produces improved fetal immobilization with good maternal sedation and only minimal effects on maternal respiration.

Fetal surgery is a clinical reality

An increasing number of fetal anomalies are being diagnosed prior to birth, some of them amenable to fetal surgical intervention. We discuss the current clinical status and recent advances in endoscopic and open surgical interventions. In Europe, fetoscopic interventions are widely embraced, whereas the uptake of open fetal surgery is much less. The indications for each access modality are different, hence they cannot substitute each other. Although the stage of technical experimentation is over, most interventions remain investigational. Today there is level I evidence that fetoscopic laser surgery for twin-to-twin transfusion syndrome is the preferred therapy, but this operation actually takes place on the placenta. In terms of surgery on the fetus, an increasingly frequent indication is severe congenital diaphragmatic hernia as well as myelomeningocele. Overall maternal safety is high, but rupture of the membranes and preterm delivery remain a problem. The increasing application of fetal surgery and its mediagenicity has triggered the interest to embark on fetal surgical therapy, although the complexity as well as the overall rare indications are a limitation to sufficient experience on an individual basis. We plead for increased exchange between high volume units and collaborative studies; there may also be a case for self-regulation. Inclusion of patients into trials whenever possible should be encouraged rather than building up casuistic experience.

Neonatal clinical pharmacology

Effective and safe drug administration in neonates should be based on integrated knowledge on the evolving physiological characteristics of the infant who will receive the drug and the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. Consequently, clinical pharmacology in neonates is as dynamic and diverse as the neonates we admit to our units while covariates explaining the variability are at least as relevant as median estimates. The unique setting of neonatal clinical pharmacology will be highlighted based on the hazards of simple extrapolation of maturational drug clearance when only based on ‘adult’ metabolism (propofol, paracetamol). Second, maturational trends are not at the same pace for all maturational processes. This will be illustrated based on the differences between hepatic and renal maturation (tramadol, morphine, midazolam). Finally, pharmacogenetics should be tailored to neonates, not just mirror adult concepts. Because of this diversity, clinical research in the field of neonatal clinical pharmacology is urgently needed and facilitated through PK/PD modeling. In addition, irrespective of already available data to guide pharmacotherapy, pharmacovigilance is needed to recognize specific side effects. Consequently, pediatric anesthesiologists should consider to contribute to improved pharmacotherapy through clinical trial design and collaboration, as well as reporting on adverse effects of specific drugs.