Median effective dose (ED50) of paracetamol and nefopam for postoperative pain: isobolographic analysis of their antinociceptive interaction.

BACKGROUND: The analgesic efficacy of nefopam and of paracetamol has been shown in the postoperative period after mild- and moderate-pain surgery. The aim of this study was to define the median effective analgesic doses of each drug and of their combination, in order to determine the nature of their interaction. METHODS: Ninety adult patients scheduled to undergo tonsillectomy under general anesthesia were enrolled in one out of three groups: nefopam group, or paracetamol group, or nefopam-paracetamol group. The median effective dose for each drug and also for their combination was defined using an up-and-down sequential allocation technique. The analgesic interaction of their combination was assessed using an isobolographic analysis. RESULTS: The median effective analgesic dose (median value and 95% confidence interval) of nefopam and paracetamol were 21.7 mg (21.1-22.3 mg) and 628 mg (600-656 mg), respectively. The median effective analgesic doses of the combination were 8.9 mg (8.7-9.1 mg) for nefopam and 265 mg (256-274 mg) for paracetamol. The isobolographic analysis demonstrated a supra-additive interaction of the two drugs. CONCLUSION: The combination of nefopam and paracetamol produces effective analgesia with a synergistic interaction.

[Femoral neck fractures in patients over 50 years old]. / Les fractures du col du fémur après 50 ans.

INTRODUCTION: Despite many papers and instructional course lectures, therapeutic guidelines are not clearly defined about treatment of femoral neck fractures. The aim of this multicentric French symposium was to prospectively study the results of current therapeutic options in order to propose scientifically proven options. MATERIAL AND METHODS: Three prospective studies were carried out in order to answer to these questions: (1) is it possible with anatomical reduction and stable fixation to lower the non union and osteonecrosis rate? (2) is functional treatment of Garden 1 fractures successful in more than 65 years patients? (3) what criteria are useful to choose the kind of arthroplasty for more than 65 years patients? RESULTS: For the 64 patients between 50 and 65 years old included in the first study, 44 ORIF and 17 prostheses were performed. No open reduction was performed in this series despite a 34% malreduction rate. The risk for displacement after functional treatment of Garden 1 fractures is 31%. For patients over 65 years old, almost fractures are treated in this series by an arthroplasty. The one-year mortality rate after displaced femoral neck fracture was 17%. Functional results were better in total hip prosthesis group than in bipolar or unipolar group. Non cemented stems were not safer than cemented ones in frail patients. DISCUSSION AND CONCLUSIONS: For young patients, ORIF should be the treatment of choice: the initial displacement and its effects on the femoral head vascularisation, the quality of reduction and fixation are the two most significant factors for good outcome. For Garden 1, fractures in patients 65 years old or more, it is proposed to performed an internal fixation despite in two thirds of the cases, it should be unnecessary because non identification of predictive factors of failure. For patients over 65 years old, the type of arthroplasty to perform in displaced fractures is to be chosen according to the preoperative mobility and comorbidities. Because of acetabular erosion with long-term follow-up, it is clearly indicated to perform total hip replacement for patients with life expectancy of 10 years or more. For frail patients, unipolar arthroplasty is the best option. The place for bipolar or uncemented implants is not yet well-defined and more prospective trials are needed. In this multicentric study, results appear quite different in terms of mortality, or functional status. These differences seem to be related to technical choice, geriatric care, nutritional consideration or surgical organisation, all factors that may be of major importance for prognostic.

[Anaesthetic preoperative assessment of chronic medications and herbal medicine use: a multicenter survey]. / Traitement médicamenteux et phytothérapie des patients adressés en consultation d'anesthésie: enquête multicentrique.

OBJECTIVE: This study was undertaken to quantify the use of chronic medication and herbal remedies in the presurgical population. STUDY DESIGN: Prospective multicenter survey. PATIENTS AND METHODS: Adult patients presenting for anaesthesia were directly asked if they were currently using chronic medication or herbal remedies. RESULTS: Among 1057 patients (age 54+/-17 yrs, woman 54%, ASA 2 [1-4], 74%) were taking one or more chronic medication. The most commonly used treatments were, in descending order angiotensin-converting enzyme inhibitors and angiotensin-II receptor blockers (15%), beta blockers (11%) and platelet inhibitors (10%). Also, 9% were taking one or more of the following herbal remedies known to interact with the perioperative period: valeriane, ginseng, ginkgo, St John's wort, echinacea and ephedra. Women and patients aged 40-70 yr were most likely to be taking a herbal product (p<0.001 and p<0.01 respectively). CONCLUSION: Chronic medication and herbal remedies are common in patients presenting for anaesthesia. Because of the potential interactions between anaesthetic drugs or techniques and such medication it is important for anaesthetists to be aware of their use.

Propofol and remifentanil for intubation without muscle relaxant: the effect of the order of injection.

BACKGROUND: Common practice in intubation without muscle relaxant is to inject the opioid drug prior to the hypnotic drug. Because remifentanil reaches adequate cerebral concentration more rapidly than does propofol, we tested the hypothesis that injection of remifentanil after propofol might lead to better intubating conditions. METHODS: Thirty ASA I-II patients scheduled for elective surgery and with no anticipated difficult intubation were enrolled in the study. Five minutes after midazolam 30 microg kg(-1), patients were randomized into two groups: group PR received propofol 2.5 mg kg(-1) followed by remifentanil 1 microg kg(-1), and group RP received remifentanil 1 microg kg(-1) followed by propofol 2.5 mg kg(-1). Intubating conditions were compared using a well-validated score, and continuous arterial pressure was recorded non-invasively. RESULTS: Compared with group RP, intubating conditions were significantly better in group PR. The mean arterial pressure decrease was more pronounced in group RP. CONCLUSIONS: We therefore conclude that in premedicated healthy patients with no anticipated risk of difficult intubation, intubating and haemodynamic conditions are better when remifentanil is injected after propofol.

Effects of tidal volume reduction in acute respiratory distress syndrome on gastric mucosal perfusion.

OBJECTIVE: This study was conducted with the aim of testing the effects of a reduction in tidal volume (V(T)) on gastric mucosal perfusion using laser-Doppler flowmetry in patients with acute respiratory distress syndrome (ARDS). DESIGN: It was designed as a prospective study. PATIENTS: Seventeen patients with ARDS were enrolled in the study. All patients were mechanically ventilated in volume-controlled mode. Before the start of the protocol, V(T) was set at 9 ml/kg body weight. INTERVENTION: V(T) was reduced to 6 ml/kg body weight. MEASUREMENTS AND RESULTS: Measurements of systemic hemodynamic parameters and gastric mucosal blood flow (GMBF) were obtained before and after reduction of V(T). Cardiac index, heaart rate and pulmonary arterial pressure increased significantly after V(T) reduction. The increase in cardiac output was observed in all patients. However, despite a mean 25% increase in cardiac output after V(T) reduction, no significant increase in mean GMBF was observed, and individual GMBF responses were heterogeneous. CONCLUSION: V(T) reduction in patients with ARDS, despite resulting in an increase in cardiac output, did not change gastric mucosal perfusion. The heterogeneity in the individual response of GMBF to V(T) reduction could be due to opposite direct (i.e., local vasodilatory effect) and indirect (i.e., global sympathetic stimulation) effects of hypercapnia on gut vessels.

[Information and anesthesia: what does the patient desire?]. / Information et anesthésie: que souhaite le patient?

OBJECTIVE: The aim of the study was to assess the patient's desire for information regarding their preoperative care and to assess the anaesthetists' perception of that desire. STUDY DESIGN: Questionnaire. METHODS: The question: "Would you like to be fully informed about" 13 topics of the perioperative management was asked to 106 patients at the time of the preoperative visit. Two answers were possible: Yes I want to know; No I don't want to know. 22 senior anaesthesists were also interviewed and were asked to speculate about the patients response to each item. Data were compared with those of a similar questionnaire used in different countries. RESULTS: One hundred patients who underwent general, orthopaedic, urologic surgery were interviewed. Patients sought information most frequently concerning: postoperative pain and postoperative recovery (88%), time for ambulation (83%), duration of anaesthesia (77%) and different methods of anaesthesia (77%). Only 63% patients desired to be informed about all possible complications of anaesthesia. Senior anaesthesists had a correct perception of patients desire for information about the 4 important items but not for the complications of anaesthesia. CONCLUSION: Our study suggests that an exhaustive information about anaesthesia is not wished by every patients.

[Coagulation abnormalities after total hip prosthesis (THP), a rare cause: antibiotic prophylaxis]. / Anomalies de la coagulation après prothèse totale de hanche (PTH), une cause rare: l'antibioprophylaxie.

A 87-year-old patient developed coagulation abnormality following hip surgery related to the prophylactic use of cefamandole. Cefamandole as others cephalosporins with a methyl-tetrazol-thiol lateral chain interferes with the vitamin K regeneration cycle as do oral anticoagulants. Therefore, the use of others antibiotics or systematic vitamin K1 supplementation or single dose of cefamandole is recommended for patients with renal failure or with malnutrition. Vitamin K1 supplementation is a simple method resulting in complete resolution of the coagulation disorder.

Effects of epinephrine, norepinephrine, or the combination of norepinephrine and dobutamine on gastric mucosa in septic shock.

OBJECTIVES: To compare in the same patient with septic shock, respective effects of epinephrine, norepinephrine, and the combination of norepinephrine and dobutamine (5 microg/kg/min) on systemic hemodynamic parameters and gastric mucosal perfusion using gastric tonometry and laser-Doppler flowmetry techniques. DESIGN: Prospective, controlled, randomized, crossover study. SETTING: University hospital intensive care unit. PATIENTS: Twelve patients with septic shock. INTERVENTIONS: Each patient received in a random succession epinephrine, norepinephrine, and norepinephrine plus dobutamine. Dosages of epinephrine and norepinephrine were adjusted to achieve a mean arterial pressure between 70 and 80 mm Hg. A laser-Doppler probe and a tonometer were introduced into the gastric lumen. MEASUREMENTS AND MAIN RESULTS: The increase in gastric mucosal perfusion detected by laser-Doppler flowmetry was higher with epinephrine and the combination of norepinephrine and dobutamine than with norepinephrine alone (p < .05). In addition, the ratio of gastric mucosal perfusion (local oxygen delivery) to systemic oxygen delivery was increased after norepinephrine plus dobutamine as compared with norepinephrine alone and epinephrine (p< .05). Although values of intramucosal pH and gastroarterial PCO2 tended to be higher with norepinephrine plus dobutamine compared with those obtained with norepinephrine and epinephrine, differences were not statistically significant. CONCLUSIONS: For the same mean arterial pressure in patients with septic shock, our study showed that administration of epinephrine increased gastric mucosal perfusion more than norepinephrine administration alone. Addition of dobutamine (5 microg/kg/ min) to norepinephrine improved gastric mucosal perfusion. This result could be explained by a vasodilating effect of dobutamine on gastric mucosal microcirculation.

Difference between arterial and end-tidal carbon dioxide pressures during laparoscopy in paediatric patients.

PURPOSE: To assess the effect of pneumoperitoneum on P(a-ET)CO2 gradient in children. METHODS: Sixty one ASA I and II children (10.7 +/- 3.0 yr, 38.4 +/- 14.2 kg, mean +/- SD), scheduled for visceral or urological laparoscopic procedures, were studied. They were anaesthetized, intubated, paralysed and their lungs ventilated with constant ventilator settings to obtain PETCO2 values between 4.3 and 4.8 kPa. Intra-abdominal pressure was maintained between 8 and 14 mmHg. The following measurements were performed at steady state, before the pneumoperitoneum (T1) and 15 min later (T2): heart rate, systolic and diastolic arterial pressure; peak airway and intra-abdominal pressure; PaCO2 corrected for the patient's temperature; PETCO2 drawn between the micropore filter and the ventilator tubes, corrected for BTPS conditions; P(a-ET)CO2. Values between -1.0 and +1.0 mmHg were considered nil; patient position (horizontal or head-down tilt): all patients were horizontal at T1. RESULTS: Arterial pressure, heart rate and peak airway pressure increased at T2: PaCO2 and PETCO2 increased by 14%. The incidence of negative gradients increased from 54 to 67% although mean P(a-ET)CO2 remained clinically unchanged. No difference was found in P(a-ET)CO2 gradient, whatever the position and intra-abdominal pressure. The 95% confidence intervals for P(a-ET)CO2 were [-5.6; +3.2] at T1 and [-8.8; +4.8] at T2. CONCLUSION: PETCO2 often overestimates PaCO2 during laparoscopy in children, by up to 8.8 mmHg. Arterial blood gas analysis should be performed during long procedures to avoid hyperventilation.

Gastric mucosal oxygen delivery decreases during cardiopulmonary bypass despite constant systemic oxygen delivery.

UNLABELLED: Previous studies report a decrease in gastric mucosal oxygen delivery during cardiopulmonary bypass (CPB). However, in these studies, CPB was associated with a reduction in systemic oxygen delivery (DO2). Conceivably, this decrease in DO2 could have contributed to the observed decrease in gastric mucosal oxygen delivery. Thus, in the present study, we assessed the effects of the maintenance of DO2 (at pre-CPB values) during hypothermic (30-32 degrees C) CPB on the gastric mucosal red blood cell flux (GMRBC flux) using laser Doppler flowmetry. In 11 patients requiring cardiac surgery, the pump flow rate during CPB was initially set at 2.4 L x min(-1) x m(-2) and was adjusted to maintain DO2 at pre-CPB values (flow 2.5-2.7 L x min[-1] x m[-2]). Despite a constant DO2, the GMRBC flux was decreased during CPB. These decreases averaged 50% +/- 16% after 10 min, 50% +/- 18% after 20 min, 49% +/- 21% after 30 min, and 49% +/- 19% after 40 min of CPB. The rewarming period was associated with an increase in GMRBC flux. Thus, maintaining systemic DO2 during CPB seems to be an ineffective strategy to improve gastric mucosal oxygen delivery. IMPLICATIONS: In the present study, we tested the hypothesis that gastric mucosal red blood cell flux assessed by laser Doppler flowmetry could be improved by maintaining baseline systemic flow and oxygen delivery during hypothermic cardiopulmonary bypass. Despite this strategy, gastric mucosal red blood cell flux decreased by 50% during hypothermic cardiopulmonary bypass.

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.

Lidocaine plasma concentrations in pediatric patients after providing airway topical anesthesia from a calibrated device.

The aim of this prospective study was to evaluate plasma lidocaine concentrations in infants and children after laryngeal spray using a calibrated device. Twenty-one patients aged 3 to 24 mo requiring laryngoscopy or bronchoscopy were included in the study. Anesthesia was induced via a mask with halothane up to 2% in 100% O2. Lidocaine was administered using a 5% lidocaine spray. For patients weighing less than 10 kg, one spray (8 mg of lidocaine) was administered. For those weighing from 10 to 20 kg, two sprays (16 mg) were given. The dose of lidocaine administered ranged between 0.9 and 2.6 mg/kg. Maximum plasma lidocaine concentration (Cmax) was 1.05 +/- 0.55 micrograms/mL (mean +/- SD; range 0.24-2.29 micrograms/mL). With this procedure, we demonstrated the safety of administering lidocaine to children by laryngeal spraying using a 5% sprayer.