[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.

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.

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.

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.

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.

[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.

Influence of timing on the analgesic effect of intravenous ketorolac after orthopedic surgery.

This study evaluated the pre-emptive analgesic effect of intravenous (i.v.) ketorolac (KET) for total hip replacement (THR). Sixty patients who underwent surgery for THR under general anesthesia were randomly allocated to 3 groups. Two i.v. injections were administered: one before induction and one after surgery. The patients were studied prospectively in a double-blind manner. The control group (CONT; n = 20) received 2 ml of normal saline (NS) for both injections. The pre-operative KET group (PRE; n = 20) received 60 mg of KET and then 2 ml of NS. The postoperative KET group (POST; n = 20) received 2 ml of NS and then 60 mg of KET. General anesthesia was standardized with a intra-operative cumulated dose of fentanyl limited to 4 micrograms/kg. In the recovery room (RR), pain was controlled with an i.v. tritration of morphine; thereafter, on the surgical ward, patients used a patient-controlled analgesia (PCA) pump (Abbott). Pain was evaluated with a visual analogue scale (VAS) at rest and movement in the RR, then every hour for 6 h and every 6 h for 5 days. The side effects monitored were: sedation, respiratory depression, nausea, perioperative bleeding. The patients and surgery were similar for the 3 groups. Upon arrival in the RR, VAS scores taken at rest and at movement were lower for the PRE group than for the CONT and POST groups. Otherwise, VAS scores were similar in all 3 groups. The cumulative dose of morphine in the PRE group was lower than that for the CONT and POST groups from 0 to 6 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of lignocaine in myocardial contusion: an experiment on rabbit isolated heart.

1. The reported incidence of myocardial contusion after blunt chest trauma varies from 16 to 76%. Of these patients, about 6% present a severe, life threatening contusion. We used an isolated heart preparation to examine the effect of lignocaine on myocardial performance after contusion. 2. Thirty hearts obtained from male New Zealand rabbits were perfused at constant flow according to the Langendorff technique and were divided into four groups. The following parameters were measured at frequent intervals for 60 min: mean coronary perfusion pressure (CPP), left ventricular diastolic pressure (LVDP), developed pressure (DP), dP/dtmax, dP/dtmin. 3. Group 1 (n = 6) served as control, group 2 (n = 7) received lignocaine for 20 min (15 microM for the first 10 min and 30 microM for the following 10 min), group 3 (n = 9) had a contusion leading to a 30-50% decrease in dP/dtmax and group 4 (n = 8) had the contusion and the lignocaine infusion was started 10 min after the contusion and stopped after 30 min. Lignocaine concentration was measured in the effluent. 4. Lignocaine alone moderately decreased contractility in group 2. In group 3, after contusion, DP, dP/ dtmax, and dP/dtmin were markedly decreased during the 60 min recording period. In group 4, lignocaine infusion rapidly restored contractility. DP, dP/dtmax and dP/dtmin returned towards their basal values. This improvement of contractility remained stable, even after lignocaine infusion was discontinued. 5. In our rabbit isolated heart preparation, lignocaine at a low therapeutic concentration was able to restore contractility after contusion. These results need to be confirmed by other studies but this may lead to promising therapeutic intervention.

Comparison of dopamine and norepinephrine after traumatic brain injury and hypoxic-hypotensive insult.

After severe brain trauma, blood-brain barrier disruption and alteration of cerebral arteriolar vasoreactive properties may modify the cerebral response to catecholamines. Therefore, the goal of the present study was to compare the effects of dopamine and norepinephrine in a model of brain injury that consisted of a weight-drop model of injury complicated by a 15-min hypoxic-hypotensive insult (HH). Sprague-Dawley rats (n = 7 in each group) received, after brain injury, an infusion of either norepinephrine (TNE group) or dopamine (TDA group) in order to increase cerebral perfusion pressure (CPP) above 70 mm Hg. In addition, a control group (C group, no trauma) and a trauma group (T group, brain injury, no catecholamine infusion) were studied. Mean arterial pressure (MAP), intracranial pressure (ICP, intraparenchymal fiberoptic device), and local cerebral blood flow (LCBF, extradural laser-Doppler fiber) were measured throughout the protocol. In T group, brain injury and HH induced a decrease in CPP (by an increase of ICP and a decrease of MAP), and a decrease of LCBF. Both norepinephrine and dopamine failed to increase CPP, and ICP was significantly higher in TNE and TDA groups than in T group. Interestingly, norepinephrine was not able to alleviate the decrease in MAP. Neither norepinephrine or dopamine could induce an increase of MAP. LCBF decreased similarly in T, TNE and TDA groups. In conclusion, norepinephrine and dopamine are not able to restore values of CPP above 70 mm Hg in a model of severe brain trauma. Furthermore, their systemic vasopressor properties are altered.

Left ventricular function after severe trauma.

OBJECTIVE: To evaluate cardiac function at the early phase of severe trauma. DESIGN: Prospective, clinical study. SETTING: Anesthesiological Intensive Care Unit. PATIENTS: 7 consecutive patients admitted after severe trauma (ISS: 38 +/- 9, mean +/- SD), without preexisting cardiac disease. INTERVENTIONS: Each patient received midazolam and sufentanyl for sedation. Right heart catheterization (Swan-Ganz) and transesophageal echocardiography (TEE) were performed. The fractional area change (FAC) of the left ventricle was calculated within 6 h following trauma and at day 1 and day 2 in order to evaluate left ventricular function. MEASUREMENTS AND RESULTS: All of the patients had a low FAC value < 50% at day 0 (43.2 +/- 2.4%, range 39-46%), which increased significantly at day 2 (52.5 +/- 4%, range 47-59%, p = 0.001), whereas heart rate and preload (assessed by left ventricular end diastolic area and pulmonary arterial occlusion pressure) were constant and afterload, assessed by systolic blood pressure, increased significantly between day 0 and day 2 (112 +/- 21 to 145 +/- 24 mmHg, p = 0.02). CONCLUSION: The initial phase of severe trauma is associated with an abnormal cardiac function, suggested by a low FAC value. This myocardial dysfunction must be taken into account for early resuscitation after severe injury.

Haemodynamic study of patients with severe sepsis during haemodialysis.

A study was performed in order to observe haemodynamic changes induced by haemodialysis in 14 patients with acute renal failure and severe sepsis. Left ventricular function, as assessed by changes in pulmonary wedge pressure and left ventricular stroke work index through plasma volume expansion, did not change during haemodialysis. Ultrafiltration-induced decreases in cardiac index provoked in 8 patients, with nearly normal initial systemic arteriolar resistance, had adequate and constant increase in their resistance (p less than 0.001), whereas 6 patients with low initial systemic arteriolar resistance did not increase their resistance and had a frequent (9/13 measurements) and significant (p less than 0.001) fall in mean aortic pressure. This abnormality of vascular tone is probably due to severe sepsis and explains why hypotension is a frequent occurrence during haemodialysis in such patients.

Relationship between intracranial pressure, mild hypothermia and temperature-corrected PaCO2 in patients with traumatic brain injury.

OBJECTIVE: To study the effects of mild hypothermia and associated changes in temperature-corrected PaCO2 (cPaCO2) on intracranial pressure (ICP), mean velocity of the middle cerebral artery (Vm), and venous jugular saturation in O2 (SjvO2) in patients with severe traumatic brain injury (TBI). DESIGN: Prospective, observational study. SETTING: Intensive care unit. PATIENTS: Severe TBI patients mechanically ventilated, sedated and paralyzed. INTERVENTIONS: Twenty patients were subjected to four consecutive periods: (a) normocapnia-normothermia; (b) hypocapnia-normothermia, where hypocapnia was induced by an increase in minute volume; (c) hypocapnia-hypothermia, where hypocapnia was induced by hypothermia maintaining the ventilatory settings constant; (d) normocapnia-hypothermia, where normocapnia was achieved by a decrease in minute volume. MEASUREMENTS AND RESULTS: cPaCO2 was 41 +/- 8 mmHg in periods 1 and 4, and 31 +/- 7 mmHg in periods 2 and 3. Core temperature was 37.1 +/- 0.8 degrees C in periods 1 and 2, and 34.1 +/- 1.1 degrees C in periods 3 and 4. End-tidal CO2 and cPaCO2 values showed no difference between periods 1 and 4 and periods 2 and 3. ICP and Vm were dependent on cPaCO2 but independent of core temperature values. SjvO2 was related to cPaCO2 and was significantly higher during period 3 than during period 2 (P < 0.05). CONCLUSION: The decrease in ICP was similar when hypocapnia was induced by hyperventilation or as a result of hypothermia alone. The relationship between cPaCO2 and ICP might predict variations in ICP during changes in core temperature. Further studies are needed to confirm the cerebral metabolic effects of moderate hypothermia in TBI patients.

Heterogeneous regional vascular responses to simulated transient hypovolemia in man.

OBJECTIVE: To describe the evolution of systemic and regional blood flows during and after hypovolemia in humans. DESIGN: Simulation of hypovolemia by a prolonged application of lower body negative pressure (LBNP). SETTING: Laboratory of Clinical Research, Surgical Intensive Care Unit of an University Hospital. PARTICIPANTS: 8 healthy male volunteers. INTERVENTIONS: 3 successive and increasing 15 min-levels of LBNP were followed by a progressive return (10 min) to atmospheric pressure, then a 60 min-recovery period. MEASUREMENTS AND MAIN RESULTS: Simulated hypovolemia induced a parallel one-third decrease in cardiac output (bioimpedance), musculocutaneous (venous plethysmography) and splanchnic (ICG clearance) blood flows. Adrenergic-mediated peripheral vasoconstriction prevented any change in mean arterial pressure. The decrease in renal blood flow (PAH clearance) was limited, glomerular filtration rate (inulin clearance) unchanged and thus filtration fraction increased. All the cardiovascular and biological variables returned to pre-LBNP values during the recovery period except for splanchnic blood flow which remained below control values 60 min after the return to atmospheric pressure. CONCLUSIONS: Since a sustained splanchnic vasoconstriction follows a transient normotensive hypovolemia in healthy men despite adequate treatment considering arterial pressure and cardiac output, the therapeutic goals of fluid resuscitation after hypovolemic shock might be revisited and a supranormal value of cardiac output proposed.

Contribution of bronchoalveolar lavage to the diagnosis of posttraumatic pulmonary fat embolism.

OBJECTIVE: To verify whether the determination of the percentage of cells recovered by bronchoalveolar lavage and containing fat inclusions is a useful diagnostic tool of posttraumatic pulmonary fat embolism. DESIGN: Prospective study. SETTING: Surgical Intensive Care Units in two university hospitals. PATIENTS: 56 successive trauma patients needing prolonged postinjury mechanical ventilation, including 4 with clinical definite fat embolism syndrome, 5 in whom the diagnosis had been clinically suspected but was impossible to confirm or exclude before bronchoscopy, and 47 with no clinical evidence of the syndrome. Control groups included 8 patients without previous trauma who developed ARDS and 6 healthy surgical patients. METHODS: Bronchoalveolar lavage was performed within the first post-traumatic 3 days in trauma patients, at the beginning of the pulmonary disease in non trauma ARDS patients and just after anesthesic induction in healthy ortopedic patients. The magnitude of lipid content in alveolar cells was compared with the clinical pattern of the pulmonary fat embolism syndrome retrospectively evaluated at the seventh day postinjury in trauma patients. RESULTS: All the patients with definite fat embolism syndrome had more than 70% of lavage cells containing fat droplets. The group of patients in whom the diagnosis of the fat embolism syndrome was suspected had percentages of fat cells above 30% in 4 out of 5 patients. A percentage of fat cells above 30% was only observed in 7 out of the 47 patients without clinical evidence of the syndrome. The percentage varied between 0% to 35% in the group of non trauma ARDS patients and between 0 to 5% in healthy surgical patients. CONCLUSION: Lipid inclusions in alveolar cells are common during traumatic and non-traumatic respiratory failure. Determination of the percentage of cells recovered by bronchoalveolar lavage and containing fat droplets may contribute to the diagnosis of the fat embolism syndrome in mechanically-ventilated trauma patients with respiratory failure provided that the significant threshold would be 30%.

Transgastric, pulsed Doppler echocardiographic determination of cardiac output.

OBJECTIVE: The aim of this study was to evaluate the accuracy of cardiac output measurement with transesophageal echocardiography (TEE) using a transgastric, pulsed Doppler method in acutely ill patients. DESIGN: Cardiac output was simultaneously measured by thermodilution (TD) and a transgastric, pulsed Doppler method. SETTING: The study was carried out in a surgical intensive care unit as part of the management protocol of the patients. PATIENTS: Thirty consecutive acutely ill patients with a Swan-Ganz catheter, mechanically ventilated, sedated and with a stable hemodynamic condition were included. MEASUREMENTS: Pulsed Doppler TEE was performed using a transgastric approach in order to obtain a long axis view of the left ventricle. Cardiac output was calculated from the left ventricular outflow tract diameter, the velocity time integral of the blood flow profile and heart rate. RESULTS: One patient was excluded because of the presence of aortic regurgitation and another, because of the impossibility of obtaining a transgastric view. Twenty-eight simultaneous measurements were performed in 28 patients. A clinically acceptable correlation and agreement were found between the two methods (Doppler cardiac output = 0.889 thermodilution cardiac output +0.74 l/min, r = 0.975, p <0.0001). CONCLUSION: Transgastric pulsed Doppler measurement across the left ventricular outflow tract with TEE is a very feasible and clinically acceptable method for cardiac output measurement in acutely ill patients.

Pharmacokinetics and absolute bioavailability of ciprofloxacin administered through a nasogastric tube with continuous enteral feeding to critically ill patients.

OBJECTIVE: To determine the pharmacokinetics and absolute bioavailability of ciprofloxacin in 12 critically ill patients receiving continuous enteral feeding. DESIGN: a prospective, cross-over study. SETTING: 12-bed surgical intensive care unit in a University Hospital. PATIENTS: 12 stable critically ill patients on mechanical ventilation and receiving continuous enteral feeding (Normoreal fibres) without diarrhea or excessive residual gastric contents ( < 200 ml/4 h). None had gastro-intestinal disease, renal insufficiency (estimated creatinine clearance > or = 50 ml/min) or was receiving medications that could interfere with ciprofloxacin absorption or metabolism. MEASUREMENTS AND MAIN RESULTS: The study was carried out after the fourth (steady state) b. i. d. intravenous (i. v.) 1-h infusion of 400 mg and the second b. i. d. nasogastric (NG) dose of 750 mg (crushed tablet in suspension). Plasma concentrations were measured by high-performance liquid chromatography. The median (range) peak concentration after i. v. infusion was 4.1 (1.5-7.4) mg/l, and that after NG administration was 2.3 (0.7-5.8) mg/l, occurring 1.25 (0.75-3.33) h after dosing. The median [range] areas under plasma concentration-time curves were similar for the two administration routes (10.3 [3.3-34.6] and 8.4 [3.6-53.4] for i.v. infusion and NG administration, respectively). Ciprofloxacin bioavailability ranges from 31 to 82 % (median, 44%). CONCLUSIONS: In tube-fed critically ill patients, a switch to the NG ciprofloxacin after initial i. v. therapy to simplify the treatment of severe infections is restricted to those for whom serial assessments of ciprofloxacin levels are routinely available.

Renal effects of low-dose dopamine during vasopressor therapy for posttraumatic intracranial hypertension.

OBJECTIVE: To investigate the effects of low-dose dopamine (Dop) on renal hemodynamics and function in patients with brain trauma receiving norepinephrine (NE). DESIGN: Prospective clinical study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 20 stable, non-septic, mechanically ventilated, sedated patients with brain trauma and normal renal function treated with intravenous NE (0.11-0.65 microg/kg per min) to maintain an adequate cerebral perfusion pressure (> 60 mmHg). INTERVENTIONS: Two successive 1-h study periods with NE alone then NE + Dop (2 microg/kg per min). During each period, creatinine (Cl(CREAT)), sodium (Cl(Na)), potassium (Cl(K)), osmolar (Cl(OSM)) and free water (Cl(H2O)), clearances were measured in all the patients. Effective renal blood flow (ERBF, para-aminohippurate clearance) and glomerular filtration rate (GFR, inulin clearance) were measured in 7 of the 20 patients. RESULTS: Dop during NE infusion induced increases in urine flow and natriuresis which were not correlated with possible changes in arterial pressure. Cl(CREAT), GFR and their difference remained unchanged, whereas ERBF tended to increase. Fractional sodium excretion [100 x (Cl(Na)/Cl(CREAT)] and C1(K) increased during Dop infusion. CONCLUSION: The mechanism of Dop-induced natriuresis during NE infusion in brain trauma patients seems mainly related to a direct tubular effect of the drug.