Long-term hepatitis E viral load kinetics in an immunocompromised patient treated with ribavirin.

Hepatitis E virus (HEV) can cause chronic infections in immunocompromised hosts. Viral kinetics in plasma and stools are poorly understood, particularly during antiviral treatment. Prolonged faecal shedding may be a concern for transmission. We describe HEV kinetics in an immunocompromised patient with prolonged faecal shedding despite undetectable viraemia on ribavirin treatment.

[Hypoxic accident during pediatric anesthesia due to an inappropriate setting of respirator]. / Accident hypoxique en anesthésie pédiatrique dû à un réglage inadapté du respirateur.

A 3-year-old child was anesthetized for ENT examination and surgery. After induction and tracheal intubation, the patient was ventilated (controlled mode). The respirator screen showed information compatible with a failure of intubation: no expired CO2, no expired flow, no alarm of high pressure limit, and no respiratory chest movement. A fall of SpO2 appeared rapidly which recovered after extubation and manual ventilation through a face mask and reintubation. The expiratory CO2 was present when the patient was ventilated manually and disappeared under controlled ventilation. The increase in the value of the maximal insufflation pressure allowed efficient ventilation with an expiratory CO2 curve and showed high ventilation pressure compatible with a bronchospasm. This case report shows that in case of bronchospasm, if the value of the maximal insufflation pressure is low, this may lead to an erroneous diagnosis of failure of intubation.

[Vitamin B12 deficiency: what's new?]. / Hypovitaminose B12: quoi de neuf?

Vitamin B12 screening is only recommended among symptomatic patients or in those with risk factors. The main cause of vitamin B12 deficiency is the food cobalamin malabsorption syndrom. Holotranscobalamin is a more reliable marker than cyanocobalamin to confirm vitamin B12 deficiency, but it has not been validated yet in complex situations. An autoimmune gastritis must be excluded in the absence of risk factors but in the presence of a probable deficiency. Oral substitution treatment is effective but requires excellent therapeutic compliance and close follow-up to monitor the response to treatment. It has not yet been studied among patients suffering from severe symptoms, inflammatory bowel disease and ileal resection.

Temporal analysis of regional anaesthesia-induced sensorimotor dysfunction: a model for understanding phantom limb.

BACKGROUND: The peripheral deafferentation induced by regional anaesthesia (RA) results in misperception of size-shape (S) and posture (P) of the anesthetized limb. During RA, most patients seem to describe motionless 'phantom limbs' fixed in stereotyped illusory positions, suggesting that RA could unmask stable postural patterns. The question of whether movement illusions exist or not after anaesthesia needs a prospective study. This study aimed to describe the phenomenology of RA-induced kinesthetic illusions (K illusions). METHODS: We examined prospectively the body image alteration during infraclavicular blocks in 20 patients. Multimodal sensory testing (pinprick, heat-cold, pallesthesia, and arthrokinesia) and assessment of motor function were performed every 5 min for 60 min after administration of the local anaesthetics. Meanwhile, patients described phantom limb sensations (S, P, and K illusions). RESULTS: We individualized the occurrence of K illusions [44 (8) min] with respect to S illusions [7 (3) min; P<0.005] and P illusions [22 (4) min; P<0.001]. A close relationship between the onset of K illusions and proprioceptive impairment (arthrokinesia: r=0.92, P<0.001; pallesthesia: r=0.89, P<0001) and abolishment of motor activity (r=0.83, P<0.001) was identified. Finally, a principal component analysis showed that S and P illusions were essentially related to the proprioceptive impairment. CONCLUSIONS: This study analyses for the first time the temporal evolution of sensorimotor dysfunction and the onset of K illusions during RA. Our results suggest the involvement of an alteration of proprioception and motor functions in the origin of this phenomenon. These data agree with the motor awareness theory.

Wakefulness and loss of awareness: brain and brainstem interaction in the vegetative state.

OBJECTIVE: The ascending reticular activating system (ARAS) modulates circadian wakefulness, which is preserved in a persistent vegetative state (PVS). Its metabolism is preserved. Impairment of metabolism in the polymodal associative cortices (i.e., precuneus) is characteristic of PVS where awareness is abolished. Because the interaction of these 2 structures allows conscious sensory perception, our hypothesis was that an impaired functional connectivity between them participates in the loss of conscious perception. METHODS: (15)O-radiolabeled water PET measurement of regional cerebral blood flow (rCBF) was performed at rest and during a proprioceptive stimulation. Ten patients in PVS and 10 controls were compared in a cross-sectional study. The functional connectivity from the primary sensorimotor cortex (S1M1) and the ARAS in both groups was also investigated. RESULTS: Compared with controls, patients showed significantly less rCBF in posterior medial cortices (precuneus) and higher rCBF in ARAS at rest. During stimulation, bilateral Brodmann area 40 was less activated and not functionally correlated to S1M1 in PVS as it was in controls. Precuneus showed a lesser degree of deactivation in patients. Finally, ARAS whose activity was functionally correlated to that of the precuneus in controls was not in PVS. CONCLUSIONS: Global neuronal workspace theory predicts that damage to long-distance white matter tracts should impair access to conscious perception. During persistent vegetative state, we identified a hypermetabolism in the ascending reticular activating system (ARAS) and impaired functional connectivity between the ARAS and the precuneus. This result emphasizes the functional link between cortices and brainstem in the genesis of perceptual awareness and strengthens the hypothesis that consciousness is based on a widespread neural network.

Hypotension during surgery for femoral neck fracture in elderly patients: effect of anaesthetic techniques. A retrospective study.

BACKGROUND: The aim of this retrospective study was to compare the incidence of hypotension between different anaesthetic techniques, including general anaesthesia (GA), spinal anaesthesia single injection (SA), continuous spinal anaesthesia with 2.5 mg bolus injections as needed (CSA 2.5) or 5 mg bolus injections as needed (CSA 5) in elderly patients (>75 yrs old) undergoing surgery for femoral neck fractures. METHODS: Demographic, surgical and hemodynamic data from 333 patients over a four year period within a single hospital were recorded and examined. RESULTS: Forty-two patients underwent GA, 109 underwent SA, 61 underwent CSA 5, and 121 underwent CSA 2.5. Patients receiving GA, SA or CSA 5 had a higher incidence of hypotension (83%, 68%, and 34%, respectively) than patients who underwent CSA 2.5 (4%; P<0.05). The CSA 2.5 group required less colloid infusion (490+/-50 mL) than the GA and SA groups (810+/-330 and 645+/-230 mL, respectively). The CSA 2.5 group also required less crystalloid infusion volume (760+/-371 mL) than the GA group (1140+/-770 mL). Ephedrine infusion was higher in the GA and SA groups (30+/-10 and 26+/-9 mg, respectively) than the CSA 2.5 (15+/-8 mg; P<0.05). CONCLUSION: This study demonstrated that CSA 2.5 causes fewer episodes of hypotension than other anaesthetic techniques for surgical repair of hip fracture in elderly patients.

Cefepime in intensive care unit patients: validation of a population pharmacokinetic approach and influence of covariables.

AIM: The purpose of our study was to define and validate a population-pharmacokinetic model including the influence of patients' characteristics on the pharmacokinetics of cefepime. PATIENTS AND METHODS: A total of 55 patients were randomized in Group 1 (34 patients, 320 cefepime concentrations) for the model building and Group 2 (21 patients, 196 cefepime concentrations) for the validation group. They received cefepime as 2 g A 2 or as 4 g continuously. The population pharmacokinetic analysis was carried out using NONMEM and a baseline model was constructed for studying the influence of demographic and biological variables. The model was then validated by a comparison of the predicted and observed concentrations in Group 2. A final model was elaborated from the whole population. RESULTS: Total clearance (CL) was significantly correlated with the serum creatinine (CREA) and the central volume of distribution (V1) was correlated with the body weight (WT). The final model was: CL = 7.14 + (-0.0133 A CREA). V1 = (-16.8) + (0.475 A WT). Q (intercompartmental clearance) = 10.5. V2 = 18.1. The mean pharmacokinetic parameters and their individual variability were: CL (8.24 l/h, 45%), V1 (20.89 l, 60%), V2 (17.95 l, 49%), total volume (38.85 l, 42%) and Q (10.56 l/h, 9%). The bias (1.07 mg/l, IC 95% = -40.46 -+42.60), precision (21.19%) and AFE (1.15) demonstrated the performance of the model. CONCLUSION: We have developed and validated a pharmacokinetic model to estimate cefepime concentrations. We showed that serum creatinine and body weight are factors that may influence the standard dose of cefepime. Our model enabled us to predict cefepime concentrations in other patients.

Pharmacokinetics of ceftazidime and cefepime in burn patients: the importance of age and creatinine clearance.

AIM: The standard dosage recommendations for beta-lactam antibiotics can result in very low drug levels in intensive care (IC) patients and burn patients in the absence of renal dysfunction. We studied the pharmacokinetic parameters and serum concentrations of ceftazidime (CF) and cefepime (CE) in burn patients and analyzed the modifications according to clinical and biological parameters and in particular age and creatinine clearance. MATERIAL AND METHODS: Two pharmacokinetic studies were carried out with daily doses of 1 g x 6 for CF (n = 17) and 2 g x 3 for CE (n = 13). Creatinine clearance (CL(CR)) was both estimated and measured. Blood was sampled at steady state after an initial and a subsequent antibiotic dose. C(max) (maximal) and C(min) (minimal) concentrations were measured by HPLC. The influence of clinical and biological data was analyzed using ANOVA, ANCOVA and stepwise multiple linear regression. RESULTS: The ratio of C(min) to the low MIC break point (4 mg/l) was lower than 4 in 52% of subjects receiving CF and in 80% of subjects receiving CE. The C(min) of CF was correlated with measured CL(CR) and was higher in mechanically ventilated patients than in non-ventilated patients. The clearance of CF was correlated with age. The C(min) of CE was correlated with age and drug clearance with measured CL(CR). Therefore dosage adjustment of these drugs in burn patients needs to take into account age, measured creatinine clearance and the danger of low concentrations occurring when the creatinine clearance is greater than 120 ml x min(-1). CONCLUSION: In burn patients, the pharmacokinetic disposition of CF and CE was much more variable than in healthy subjects. Age and CL(CR) were predictors of the disposition of these antibiotics. Shortening the dosage interval or using continuous infusions will prevent low serum levels and keep trough levels above the MIC for longer periods of time. In view of the lack of a bedside measurement technique for ceftazidime and cefepime levels, we suggest a more frequent use of measured CL(CR) in order to attain efficacious clinical concentrations.

Assessment of renal function in clinical practice at the bedside of burn patients.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * In burn patients it has been shown ([2]), that there is a correlation between the creatinine clearance (CL(CR)) and the clearance of inulin. * The CL(CR) has never been studied in burn patients who have normal serum creatinine. * The Robert, Kirkpatrick and sMDRD formulae have never been evaluated in burn patients. WHAT THIS STUDY ADDS: * Despite burn patients having normal serum creatinine concentrations, the study showed that there are large variations in CL(CR) which cannot be detected by single serum creatinine measurements, and which have important implications for drug therapy. * It showed that the formulae currently used to calculate creatinine clearance on the basis of serum creatinine are inadequate for use in burn patients, and they should be abandoned in favour of direct measurement from a 24 h urine collection. AIMS: The aim of this study was to evaluate whether the renal function of burn patients could be correctly assessed using a single serum creatinine measurement, within normal limits, and three prediction equations of glomerular filtration taking into account, serum creatinine, age, weight and sex. METHODS: This was a prospective study comprising 36 adult burn patients with a serum creatinine <120 micromol l(-1), within the second or third week following the burn injury. Renal function was assessed using serum creatinine, 24 h urinary CL(CR), and the Cockcroft-Gault, Robert, Kirkpatrick and simplified MDRD equations. RESULTS: Despite normal serum creatinine concentrations in all patients, a significant number had a decreased CL(CR). The urinary CL(CR) was <80 ml(-1) min(-1) 1.73 m(-2) in nine patients (25%), and <60 ml(-1) min(-1) 1.73 m(-2) in five patients (14%). Between the groups having a CL(CR) lower or greater than 80 ml(-1) min(-1) 1.73 m(-2) there were no differences in gender, burn indices, percentage of mechanically ventilated patients or length of hospital stay, but a difference in age. The highest CL(CR) (>140 ml(-1) min(-1) 1.73 m(-2)) was found in 13 patients younger than 40 years. Regression analysis, residual and Bland-Altman plots revealed that neither the Cockcroft-Gault, Robert, Kirkpatrick nor sMDRD equations were specific enough for the assessment of renal function. CONCLUSIONS: In burn patients with normal serum creatinine during the hypermetabolic phase, serum creatinine and creatine based predictive equations are imprecise in assessing renal function.

[Multiresistant Escherichia coli meningitis after transrectal prostate biopsy]. / Méningite à Escherichia coli multirésistant après biopsie de prostate transrectale.

Transrectal prostate biopsy represents the most accurate technique to diagnose prostate cancer. More vigilance is necessary when fluoroquinolones are given as prophylactic agents because of the increase in Escherichia coli resistant strains. We report a case of multiresistant E. coli meningitis after transrectal biopsy resulting in the death of the patient.

Difficult intubation in thyroid surgery: myth or reality?

Thyroid surgery is considered to be a risk factor for difficult airway management. We prospectively studied 324 consecutive patients undergoing thyroid surgery to investigate the incidence of difficult intubation as evaluated by the intubation difficulty scale as well as other specific predictive factors. The overall incidence of difficult intubation was 11.1% (95% CI: 7.6-14.5). Median intubation difficulty scale was 0 (25th-75th percentile: 0; 2.7). In three predefined groups (no echographic goiter, clinically palpable goiter, and impalpable goiter), difficult intubation occurred in 10% (95% CI: 4.8-17.4), 13% (95% CI: 6.5-18.4), and 11% (95% CI: 4.7-16.8) of patients, respectively, with no statistical difference among the groups. Specific predictive criteria (palpable goiter, endothoracic goiter, airway deformation, airway compression, or thyroid malignancy) were not associated with an increased rate of difficult intubation. Classical predictive criteria (mouth opening <35 mm, Mallampati III or IV, short neck, neck mobility <80 degrees , thyromental distance <65 mm, and a retrognathic mandible) were significantly reliable in the univariate analysis as risk factors for difficult intubation.

[Subarachnoidal haemorrhage and myocardial failure: interest of cardiac and cerebral monitoring]. / Hémorragie méningée et défaillance myocardique: intérêt du monitorage hémodynamique par doppler oesophagien.

Spontaneous subarachnoidal haemorrhage can be associated with neurogenic pulmonary oedema and cardiogenic shock. The presentation is an ischemic myocardial dysfunction associated with normal coronary arteries. Hypoxaemia associated with arterial hypotension on patients with brain injury can worsen neurological outcome. The administration of norepinephrine associated with fluid expansion could be deleterious on cardiac function. We report the case of a patient with acute pulmonary oedema associated with post-aneurysmal subarachnoid haemorrhage managed with transoesophageal Doppler monitoring.

Increased amikacin dosage requirements in burn patients receiving a once-daily regimen.

Altered pharmacokinetics in burn patients may affect antibiotic plasma concentrations. Typical once-daily dosing (ODD) of 15 mg/kg amikacin (AMK) in burn patients does not always produce peak concentrations (C(max)) reaching the therapeutic objective of six to eight times the minimal inhibitory concentration (MIC). We recorded plasma concentrations following administration of 20 mg/kg AMK in burn patients and studied factors affecting pharmacokinetics. Mean C(max) was 48.3+/-10.8 mg/L and the C(max)/MIC ratio was 6+/-1.35. Statistical analysis demonstrated a relationship between C(max) and the area of the burn and Unit Burn Standard, and between AMK clearance and creatinine clearance (Cl(CR)). We conclude that ODD regimens of AMK in patients with burns >15% body surface area and/or with Cl(CR) >120 mL/min could require doses >20 mg/kg to reach adequate C(max). In all cases, patient therapeutic drug monitoring is essential to ensure the safe usage of these dosing recommendations.

A randomized study comparing the efficacy and safety of nadroparin 2850 IU (0.3 mL) vs. enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism after colorectal surgery for cancer.

BACKGROUND: The optimal thromboprophylactic dosage regimen of low-molecular-weight heparins in high-risk general surgery remains debatable. OBJECTIVES: We performed a randomized, double-blind study to compare the efficacy and safety of nadroparin 2850 IU (0.3 mL) and enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism (VTE) after colorectal surgery for cancer. PATIENTS AND METHODS: Patients undergoing resection of colorectal adenocarcinoma were randomized to receive once daily either 2850 IU nadroparin or 4000 IU enoxaparin s.c. for 9 +/- 2 days. The primary efficacy outcome was the composite of deep vein thrombosis (DVT) detected by bilateral venography or documented symptomatic DVT or pulmonary embolism up to day 12. The main safety outcome was major bleeding. A blinded independent committee adjudicated all outcomes. RESULTS: Out of 1288 patients analyzed, efficacy was evaluable in 950 (73.8%) patients. The VTE rate was 15.9% (74/464) in nadroparin-treated patients and 12.6% (61/486) in enoxaparin-treated patients, a relative risk of 1.27 (95% confidence interval; CI: 0.93-1.74) that did not met the criterion for non-inferiority of nadroparin. The rate of proximal DVT was comparable in the two groups (3.2% vs. 2.9%, respectively), but that of symptomatic VTE was lower in nadroparin-treated patients (0.2% vs. 1.4%). There was significantly (P = 0.012) less major bleeding in nadroparin- than in enoxaparin-treated patients (7.3% vs. 11.5%, respectively). CONCLUSION: Compared with those receiving enoxaparin 4000 IU, patients treated with nadroparin 2850 IU showed a higher incidence of asymptomatic distal DVT, but a lower incidence of symptomatic VTE. Nadroparin treatment was safer in terms of bleeding risk.

[Decompressive craniectomy and intracranial hypertension]. / Craniectomie décompressive et hypertension intracrânienne.

Decompressive craniectomy was purposed for the treatment of refractory intracranial hypertension after head injury. This review discusses results obtained by this surgery in severe head trauma. Several studies have confirmed a reduction in intracranial pressure secondary to decompressive craniectomy. Mortality decreased and the proportion of good outcome of the survivors increased. These results have not been confirmed prospectively, and indications have to be clarified. The positive effects of decompressive craniectomy compared to barbiturate or hypocapnia in the "second tier therapy" in refractory intracranial hypertension could be interesting to evaluate.

Double- vs. single-injection infraclavicular plexus block in the emergency setting: higher success rate with lower volume of local anaesthetic.

BACKGROUND AND OBJECTIVES: Infraclavicular plexus block has many advantages of particular interest in the emergency setting. However, the number of nerve stimulations needed to optimize the technique remains unclear. We evaluated both the local anaesthetic requirement and the success rate of Sim's derived infraclavicular plexus block performed with a nerve stimulator when either one or two responses were sought. METHODS: In this prospective study, 50 patients who presented for distal upper limb surgery were randomized into two groups: in Group 1, ropivacaine 0.75% 40 mL was injected when nerve stimulation elicited a distal motor response (median, ulnar or radial). In Group 2, only 30 mL of the same local anaesthetic was injected, 7 mL to the musculocutaneous nerve and 23 mL to the median, ulnar or radial nerves. Sensory and motor blocks were tested at 5-min intervals over 30 min. RESULTS: The time to perform the block was similar in both groups. The success rate of the block increased from 80% in the single-stimulation group to 92% in the double-stimulation group (not significant). The onset time of sensory and motor block was shorter and block extension was greater in ulnar, antebrachial cutaneous and brachial cutaneous nerve distributions in the multistimulation group (P < 0.05). CONCLUSIONS: We conclude that only 30 mL of local anaesthetic seems to be sufficient to ensure a high level of success when performing an infraclavicular block with stimulation of both the musculocutaneous nerve and median, ulnar or radial nerve.