Pharmacokinetic Model for Cefuroxime Dosing during Cardiac Surgery under Cardiopulmonary Bypass.

Cefuroxime (CXM) is an antibiotic recommended for surgical site infection prevention in cardiac surgery. However, the dosing regimens commonly used do not sustain therapeutic concentrations throughout surgery. The aim of this study was to conduct a population analysis of CXM pharmacokinetics (PK), and to propose an optimized dosing regimen. Adult patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) received a 1,500 mg CXM intravenous bolus followed by a 750 mg bolus at CPB priming, then every 2 h thereafter. Model-based PK simulations were used to develop an optimized dosing regimen and evaluate its efficacy in attaining various concentration thresholds, including those recommended in US and European guidelines. In total, 447 CXM measurements were acquired in 50 patients. A two-compartment model best fit the data, with total body weight and creatinine clearance determining interpatient variability in the central and peripheral volumes of distribution, and in elimination clearance, respectively. Using our optimized dosing regimen, different dosing schemes adapted to body weight and renal function were calculated to attain total concentration thresholds ranging from 12 to 96 mg/liter. Our simulations showed that the dosing regimens recommended in US and European guidelines failed to maintain concentrations above 48 mg/liter. Our individualized dosing strategy was capable of ensuring therapeutic CXM concentrations conforming to each target threshold. Our model yielded an optimized CXM dosing regimen adapted to body weight and renal function, and sustaining therapeutic concentrations consistent with each desired threshold. The optimal target concentration and necessary duration of its maintenance in cardiac surgery still remain unclear.

Overuse of preoperative laboratory coagulation testing and ABO blood typing: a French national study.

Background: Following publication of guidelines on routine preoperative tests, the French Society of Anaesthesiology and Intensive Care (SFAR), in association with French national public health insurance, conducted a survey to evaluate adherence to guidelines and the economic consequences. Methods: Using the French Hospital Discharge Database and National Health Insurance Information system, tests performed during the 30 days before surgery were analysed for two situations: (1) standard laboratory coagulation tests and ABO blood typing in children able to walk and scheduled for tonsillectomy/adenoidectomy; and (2) ABO blood typing in adults before laparoscopic cholecystectomy, thyroidectomy, lumbar discectomy or breast surgery. Guidelines do not recommend any preoperative tests in these settings. Results: Between 2013 and 2015, a coagulation test was performed in 49% of the 241 017 children who underwent tonsillectomy and 39% of the 133 790 children who underwent adenoidectomy. A similar pattern was observed for ABO blood typing although re-operation rates for bleeding on the first postoperative day were very low (0.12-0.31% for tonsillectomy and 0.01-0.02% for adenoidectomy). Between 2012 and 2015, ABO blood typing was performed in 32-45% of the 1 114 082 patients who underwent one of the four selected procedures. The transfusion rate was very low (0.02-0.31%). The mean cost for the four procedures over the 4 yr period was €5 310 000 (sd €325 000). Conclusions: Standard laboratory coagulation tests and ABO blood typing are still routinely prescribed before surgery and anaesthesia despite current guidelines. This over-prescription represents a high and unnecessary cost, and should therefore be addressed.

Ultrasonographic gastric volume before unplanned surgery.

We aimed to measure gastric antral cross-sectional area with ultrasound and estimate the gastric volume of 300 patients before unplanned surgery, fasted for at least six hours. Measurements were successfully recorded in 263 semi-recumbent patients. The median (IQR [range]) area was 333 (241-472 [28-1803]) mm2 and the mean (SD) estimated volume was 45.8 (34.0) ml. The area exceeded 410 mm2 in 92/263 (35%) measurements. Body mass index and morphine administration were associated with larger gastric areas on multivariable linear regression analysis, with beta coefficient (95%CI) 0.02 (0.01-0.04), p = 0.01, 0.23 (0.01-0.46), p = 0.04, respectively. Fasting time was not associated with gastric area and therefore could not substitute for ultrasound measurements in this cohort.

Tissue near infra red spectroscopy change is not correlated with patients' outcome in elective cardiac surgery.

BACKGROUND: Microcirculatory disturbances following cardiac surgery with cardiopulmonary bypass (CPB) are thought to be at the origin of organ dysfunction, although few studies have correlated microvascular alterations with outcome. We aimed to assess the microcirculation with near infrared spectroscopy (NIRS) and correlate NIRS parameters with intensive care length of stay and organ dysfunction. METHODS: Forty patients at increased risk of postoperative systemic inflammatory response syndrome after an elective cardiac surgery with CPB were included in this prospective observational study. Microcirculation of the thenar eminence was analysed by NIRS technology, through the tissue oxygen saturation (StO2 ) and the recovery slope after an ischaemic challenge. Organ dysfunction was assessed with the Sequential Organ Failure Assessment (SOFA) score. Microcirculation parameters were recorded at baseline, at different time points during the surgery and the first 48 postoperative hours. RESULTS: StO2 at baseline was 82% and decreased significantly until 77% at 2 h after CPB. Recovery slope values were 4.3% per second at baseline and decreased to 2.5% per second during CPB (P < 0.05). From 12 h after CPB time point, both parameters were not statistically different from baseline anymore. We found no correlation between microcirculatory parameters and mean arterial pressure, cardiac index, intensive care unit (ICU) length of stay or SOFA score. CONCLUSION: This study confirms, through a non-invasive technology, a significant but transient alteration of the microcirculation during elective cardiac surgery. However, as these microvascular alterations were not correlated with patient's outcome, NIRS-derived parameters seem to be of limited interest in the cardiac surgery setting.

Haemodynamic consequences of etomidate administration in elective cardiac surgery: a randomized double-blinded study.

BACKGROUND: The consequences of inhibition of cortisol synthesis by a single dose of etomidate on subsequent vasopressor drug usage and the duration of relative adrenal insufficiency (RAI) after cardiac surgery are not known. METHODS: This was a prospective, randomized, double-blinded controlled trial of 100 patients undergoing elective cardiac surgery and receiving either etomidate or propofol at induction of anaesthesia. A short corticotropin test was performed 12, 24, and 48 h after anaesthesia induction. RAI was defined as a response <250 nmol litre(-1). RESULTS: The mean (sd) norepinephrine infusion rate during the first 48 postoperative hours was 0.11 (0.01) and 0.11 (0.01) µg kg(-1) min(-1) in the etomidate and propofol groups, respectively (P=0.89). Time to norepinephrine withdrawal was similar between the groups. The incidence of RAI was higher in the etomidate group at 12 h (100% vs 41%, P<0.001) and 24 h (85% vs 25%, P<0.001). CONCLUSIONS: A single bolus of etomidate blunts the hypothalamic-pituitary-adrenal axis response for more than 24 h in patients undergoing elective cardiac surgery, but this was not associated with an increase in vasopressor requirements.

Population pharmacokinetic model of cefazolin in total hip arthroplasty.

Cefazolin is an antibiotic recommended for infection prevention in total hip arthroplasty (THA). However, the dosing regimen necessary to achieve therapeutic concentrations in obese patients remains unclear. The aim of this study was to conduct a population analysis of cefazolin pharmacokinetics (PK) and assess whether cefazolin administration should be weight adapted in THA. Adult patients undergoing THA surgery received an injection of 2000 mg of cefazolin, doubled in the case of BMI > 35 kg/m2 and total body weight > 100 kg. A population PK study was conducted to quantify cefazolin exposure over time compared to the therapeutic concentration threshold. A total of 484 cefazolin measurements were acquired in 100 patients, of whom 29% were obese. A 2-compartment model best fitted the data, and creatinine clearance determined interpatient variability in elimination clearance. Our PK simulations using a 2000 mg cefazolin bolus showed that cefazolin concentrations remained above the threshold throughout surgery, regardless of weight or renal function. A 2000 mg cefazolin single injection without adaptation to weight or renal function and without intraoperative reinjection was efficient in maintaining therapeutic concentrations throughout surgery. The optimal target concentration and necessary duration of its maintenance remain unclear.

Tranexamic acid in hip fracture surgery: a randomized controlled trial.

BACKGROUND: Hip fracture surgery may be associated with substantial blood loss. This study was designed to assess the efficacy and safety of the use of tranexamic acid in hip fracture surgery for the reduction of erythrocyte transfusion. METHODS: The study pertains to a randomized double-blind study with blinded adjudication of outcomes. Patients requiring surgery for an isolated hip fracture of less than 48 h received saline or tranexamic acid 15 mg kg(-1) given at skin incision and 3 h later. Primary efficacy outcome was erythrocyte transfusion from surgery up to day 8. Transfusion was administered according to a standardized protocol (Hb<9 g dl(-1)). Safety criterion was a composite of symptomatic and asymptomatic vascular events up to 6 weeks. RESULTS: Fifty-seven patients were randomized to tranexamic acid and 53 to placebo. The rate of erythrocyte transfusion was 42% with tranexamic acid and 60% with placebo (P=0.06). Preoperative haemoglobin value, age, and type of surgery were risk factors for erythrocyte transfusion independent of treatment group. The probability of vascular events at 6 weeks was 16% in the tranexamic acid group and 6% in the placebo group (P=0.10). A meta-analysis combining this study with previous trials showed that tranexamic acid significantly reduced erythrocyte transfusion in hip fracture surgery although efficacy was lower than that observed in hip or knee arthroplasty. CONCLUSIONS: In hip fracture surgery, tranexamic acid reduces erythrocyte transfusion but may promote a hypercoagulable state. Thus, further evaluation of safety is required before recommending the off-label use of tranexamic acid.

Effect of mandibular nerve block on postoperative analgesia in patients undergoing oropharyngeal carcinoma surgery under general anaesthesia.

BACKGROUND: Postoperative analgesia after oropharyngeal carcinoma surgery remains poorly studied. This study investigates the effects of mandibular nerve block (MNB) with ropivacaine 10 mg ml(-1) in conjunction with general anaesthesia (GA) on postoperative analgesia after partial glossectomy or transmandibular lateral pharyngectomy. METHODS: In a randomized double-blind study, 42 patients (21 in each group) received an MNB by the lateral extra-oral approach (MNB group) or a deep s.c. injection of normal saline (control group). Both groups received a standardized general anaesthetic. Postoperative analgesia included fixed dose of i.v. acetaminophen and morphine via a patient-controlled analgesia device. Consumption of morphine and supplemental analgesics and pain scores at rest were measured. RESULTS: The mean cumulative morphine consumption was reduced by 56 and 45% at 12 and 24 h after operation in the MNB group. The administration of analgesic rescue medications was delayed in the MNB group. The visual analogue scale (VAS) pain scores were comparable in the two groups during the first 24 h. Adequate analgesia (mean VAS < or = 3) was observed throughout the study period in the MNB group, but only from 4 h after operation onwards in the control group. The number of patients who experienced severe pain (VAS > 7) during the first postoperative day was lower in the MNB group than in the control group (3 vs 10. respectively, P < 0.05). CONCLUSIONS: In this study, MNB performed before GA for oropharyngeal carcinoma surgery improved postoperative analgesia, resulting in reduced morphine consumption at 24 h and severe pain in fewer patients.

[A case of delayed fat embolism after a vertebral osteosynthesis]. / A propos d'un cas d'embolie graisseuse pulmonaire différée post-ostéosynthèse vertébrale.

A 37-year-old woman presented an acute respiratory distress syndrome six days after a post-traumatic vertebral osteosynthesis. First, a pulmonary embolism was suspected, and a thrombolysis realised. This diagnosis was secondary excluded, and the diagnosis of probable fatty embolism was established by the bronchoalveolar lavage. So, this case shows a delayed presentation of fatty embolism and permits a discussion about clinical presentation, and diagnosis methods of such pathology.

[Which doses of anaesthetic agents in centenarian patients? Interest of BIS monitoring]. / Posologies des agents anesthésiques chez le centenaire ? Intérêt du monitorage par le BIS.

A 106-year-old female underwent emergency colectomy for peritonitis secondary to ischemic colitis. Following induction of anaesthesia with 18 mg etomidate (0,4 mg/kg), BIS monitoring allowed to perform surgery with an averaged desflurane end-tidal concentration and remifentanil infusion as low as 0.9% and 0.057 microg/kg/minute respectively. The mean BIS value was of 45+/-4 (min = 38, max = 50), systolic arterial pressure was maintained within+/-10% of control values during 72% of anaesthesia duration (160 min) and the maximal drop did not exceed 27%. No adrenergic agent was used. This observation underlined the interest of BIS when anaesthetic requirement are difficult to estimate rapidly.

Wavelet transform to quantify heart rate variability and to assess its instantaneous changes.

Heart rate variability is a recognized parameter for assessing autonomous nervous system activity. Fourier transform, the most commonly used method to analyze variability, does not offer an easy assessment of its dynamics because of limitations inherent in its stationary hypothesis. Conversely, wavelet transform allows analysis of nonstationary signals. We compared the respective yields of Fourier and wavelet transforms in analyzing heart rate variability during dynamic changes in autonomous nervous system balance induced by atropine and propranolol. Fourier and wavelet transforms were applied to sequences of heart rate intervals in six subjects receiving increasing doses of atropine and propranolol. At the lowest doses of atropine administered, heart rate variability increased, followed by a progressive decrease with higher doses. With the first dose of propranolol, there was a significant increase in heart rate variability, which progressively disappeared after the last dose. Wavelet transform gave significantly better quantitative analysis of heart rate variability than did Fourier transform during autonomous nervous system adaptations induced by both agents and provided novel temporally localized information.

[Effects of midazolam on respiratory drive in healthy volunteers]. / Effets du midazolam sur la commande ventilatoire chez le volontaire sain.

OBJECTIVE: To compare the effects of a sedative dose of midazolam on mean inspiratory flow (VT/TI = index of central respiratory activity), known as being decreased by midazolam and the intercostal muscle activity, known as being increased by this agent. STUDY DESIGN: Laboratory study. PATIENTS: Seven healthy volunteers. METHODS: After assessment of baseline values of ventilatory variables and intercostal electromyographic activity (in arbitrary units), midazolam 0.1 mg.kg-1 was administered by iv route. The measurements were repeated after 5 and 10 min, and finally 2 min after the i.v. injection of flumazenil 1 mg. RESULTS: Midazolam decreased VE and VT. Similarly VT/TI ratio decreased from 0.44 +/- 0.04 (baseline value) to 0.26 +/- 0.03 (5 min) and 0.3 +/- 0.03 L.s-1 (10 min later) respectively (P < 0.05). Conversely, midazolam increased the intercostal electromyographic activity from 4.0 +/- 0.7 (baseline value) to 26.5 +/- 16.6 (5 min) and 28.4 +/- 16.6 U (10 min later) respectively (P < 0.05). Within 2 min after flumazenil administration all variables returned to baseline values. CONCLUSIONS: The decrease of VT/TI ratio is probably linked to increased resistances in the upper airways. This ratio cannot act as an indicator of respiratory drive during sedation or anaesthesia. The assessment of the ventilatory effects of benzodiazepines must be based simultaneously of the various other indicators of the ventilatory drive, as these agents act on the different stages of the ventilatory cycle and therefore cannot be characterized by a unique variable.

[Neurotoxic role of glycocolle and derivatives in transurethral resection of the prostate]. / Rôle neurotoxique du glycocolle et de ses dérivés au cours de la résection transuréthrale de la prostate.

72-year-old patient underwent an elective transurethral resection of the prostate (TURP) performed with a spinal anaesthesia. The irrigation solution contained glycine at a concentration of 15 g.l-1. The patient's level of consciousness deteriorated over the next 4 hours. He went in an areflexic coma with pupillary areflexia and left mydriasis. The diagnosis of TUR syndrome was substantiated by a sodium blood concentration of 98 mmol.l-1, an osmotic gap of 48 mosmol.kg-1 and blood ammonia at 415 mumol.l-1. To investigate the pathophysiological role of glycine and its metabolites, their concentrations were measured by chromatography and spectrometry in plasma and CSF 8, 24 and 48 hours postoperatively. Glycine and its metabolites (serine, alanine, glyoxylic acid and glycolic acid) accumulated during the postoperative period in both blood and CSF. The central nervous system is in direct contact with these neurotropic compounds. Glycine is an inhibitory neurotransmitter, whereas glyoxylic acid and glycolic acid are considered as to be neurotoxic.

[Target controlled infusion (TCI) anesthesia using propofol. Assessment of training and practice in the operating room]. / Anesthésie intraveineuse à objectif de concentration (Aivoc) avec le propofol. Evaluation des formations et pratiques au bloc opératoire.

OBJECTIVE: To evaluate overall awareness of TCI and the need for training in the TCI technique. To assess, among trained anaesthetists, the value of the session and the impact of TCI technique on their working practice. STUDY DESIGN: Two prospective domestic surveys during the first quarter of 1999. METHODS: Three hundred anaesthetists representative of French anaesthetists as a whole, and 336 anaesthetists who had taken part in a training course. RESULTS: The notoriety of TCI was high and greater in the public sector compared with the private sector. Almost 3/4 of anaesthetists believed that training was necessary but only four anaesthetists out of ten TCI users said they had taken part in training sessions. After the training session nine anaesthetists out of ten became TCI users and would have recommended the training course despite the low number and variety of anaesthetic procedures observed during the practical part of training. The main difficulties reported during initial use were the choice of target concentrations and the management of drug interactions. Familiarisation to the technique was rapid (less than 20 procedures). Despite the lack of long experience (< 6 months for more than 2/3 of them), TCI appeared to be more likely used for anaesthesia of average duration. CONCLUSIONS: TCI was perceived to be an innovative concept with a requirement of a specific training. This preliminary appraisal of training sessions was generally satisfactory but underline a need for future training sessions focused on practical aspects.

[Postoperative dissection of the vertebral artery in two steps]. / Dissection postopératoire de l'artère vertébrale en deux temps.

The diagnosis of perioperative vertebral artery dissection can be difficult because of non-specific clinical signs. We report a case revealed by a tegmento-thalamic stroke after an abdominal second surgical look. The interest of this observation is related to a particular evolution in two steps separated by a 2-month-interval and an intercurrent cervical manipulation. After the second anesthesia, neck pain associated with a third cranial nerve palsy and a supranuclear ophtalmoplegia revealed a tegmento-thalamic ischemic stroke due to vertebral artery dissection. We discuss here the different factors possibly involved in the pathophysiology of postoperative vertebral artery dissection: positioning, cervical manipulation, subclavian central venous access and cisplatin toxicity. Vertebral artery dissection should be discussed in case of postoperative neck pain, especially with non-typical symptomatology.

[Locating the cricothyroid membrane in learning phase: value of ultrasonography?]. / Repérage de la membrane cricothyroïdienne en phase d'apprentissage: valeur ajoutée de l'échographie ?

OBJECTIVES: Emergency cricothyroidotomy is recommended as life-saving maneuver when mask ventilation and tracheal intubation are impossible. It requires the puncture of the cricothyroid membrane (CTM) whose clinical identification is difficult. The objective of this study is to evaluate if ultrasound can help locating the CTM by comparing palpation and ultrasonographic evaluation. PATIENTS AND METHODS: After ultrasound localization of CTM by a referent physician in two overweight volunteers, twelve residents without prior anatomy recall, defined by palpation an entry point for CTM. After a rapid training in CTM ultrasound localization, residents identified an ultrasound-guided puncture point. For each puncture site were registered: relevance, time and ease to localization. Six months later, residents renewed clinical and ultrasound identification of CTM on the same subjects. RESULTS: The CTM was accurately identified by palpation and ultrasound by 46% and 100% of residents respectively (P<0.05). Six months later, residents remained more effective identifying CTM with ultrasound than with palpation (78% vs. 33%) (P<0.05). Time to localization of CTM by palpation in the 2 volunteers was 15 s [11-18] and 24 s [9-39] (average [CI 95%]) whereas it was 21 s [16-25 s] and 28 s [19-36] by ultrasound respectively (ns). The ultrasound identification of CTM was also considered easier than clinical identification. CONCLUSION: Following a limited training phase, ultrasound allowed a more effective localization of CTM by residents when compared to clinical palpation in overweight patients. This benefit remained significant when assessment was repeated 6 months later.

[Process, procedure and requested conditions for academic appointment in anesthesia and intensive care]. / Processus, procédures et critères d'évaluation conduisant à la mise sur la liste d'aptitude aux fonctions de Maître de conférences des universités--praticien hospitalier (MCU-PH) et de professeur des universités--praticien hospitalier (PU-PH) en anesthésie-réanimation.

Since several decades, anesthesia care and intensive care, as well, are engaged in the way of excellence in clinical care and research. This requirement is also applied for the selection of professor and academic workers. The goals of this article are twice: first to diffuse this knowledge at the medical community and second to describe in details the long process leading to the final appointment.

[Controversies in neuroanaesthesia: positioning in neurosurgery]. / Controverses en neuroanesthésie-réanimation: les positions en neurochirurgie.

Positioning of the neurosurgical patient has several features such as the existence of specific positions (i.e: sitting, prone hyperlordotic, crouching ou kneeling positions) or the range of facilities for the same surgical indications. The last point, a source of controversy, is the subject of this review. Current indications for the sitting position, positioning for lumbar spine surgery and prevention of eye injuries are successively addressed.

[Microcirculatory dysfunction after cardiac surgery: Interest of NIRS technology with two case reports]. / Dysfonction microcirculatoire lors de la chirurgie cardiaque : intérêt de la technique NIRS à propos de deux cas cliniques.

Near infrared spectroscopy (NIRS) seems to be an interesting technology to study microcirculatory dysfunction. These alterations have been described after cardiac surgery under cardiopulmonary bypass. We report two case study reports with monitoring of StO(2) and reperfusion slope after an ischemic challenge. These two parameters are early altered notably in case of cardiac dysfunction (decrease of StO(2) and reperfusion slope). We discuss the interest of microcirculatory measurement in this context.