Pharmacokinetics of remifentanil and its major metabolite, remifentanil acid, in ICU patients with renal impairment

Background. The pharmacokinetics of remifentanil, an opioidanalgesic metabolized by non-specific esterases, and its principalmetabolite, remifentanil acid (RA), which is excreted via thekidneys, were assessed as part of an open-label safety studyin intensive care unit (ICU) patients with varying degrees ofrenal impairment. Methods. Forty adult ICU patients with normal/mildly impairedrenal function (creatinine clearance [CL_cr] 62.9 (SD) 14.5 mlmin^–1; n=10) or moderate/severe renal impairment (CL_cr14.7 (15.7) ml min^–1; n=30) were included. Remifentanilwas infused for up to 72 h, at a starting rate of 6–9µg kg^–1 h^–1 titrated to achieve a target sedationlevel, with additional propofol (0.5 mg kg^–1 h^–1)if required. Intensive arterial sampling was performed for upto 72 h after infusion. Pharmacokinetic parameters obtainedby simultaneous modelling of remifentanil and RA data were statisticallycompared between the two groups. Results. Remifentanil pharmacokinetics were not significantlyaffected by renal status. RA clearance in the moderate/severegroup was reduced to about 25% that of the normal/mild group(41 (29) vs 176 (49) ml kg^–1 h^–1, P<0.0001).Metabolic ratio, a predictor of the ratio of RA to remifentanilconcentrations at steady state, was approximately eight-foldhigher in the moderate/severe group relative to the normal/mildgroup (116 (110) vs 15 (4), P<0.0001). Maximum RA levelsapproached 700 ng ml^–1 in the moderate/severe group. Conclusions. Although RA accumulates in patients with moderate/severerenal impairment, pharmacokinetic modelling predicts that RAconcentrations during a 9 µg kg^–1 h^–1 remifentanilinfusion for up to 15 days would not exceed those reported inthe present study, for which no associated prolongation of µ-opioideffects was observed. Br J Anaesth 2004; 92: 493–503     

Severe Cerebral Venous and Sinus Thrombosis: Clinical Course,Imaging Correlates,and Prognosis

Background

Severe cerebral venous-sinus thrombosis (CVT) is a rare disease, and its clinical course, imaging correlates, as well as long-term prognosis have not yet been investigated systematically.

Methods

Multicenter retrospective study. Inclusion criteria were CVT, Glasgow coma scale ≤9, and treatment in the intensive care unit. Primary outcome was death or dependency, assessed by a modified Rankin Score (mRS) >2 at last follow-up.

Results

114 patients were included. At last follow-up (median 2.5 years), 38 patients (33.3 %) showed no or minor residual symptoms (mRS = 0 or 1), 12 (10.5 %) had a mild (mRS = 2), 13 (11.4 %) a moderate (mRS = 3), 12 (10.5 %) a severe disability (mRS = 4 or 5), and 39 (34.2 %) had died. In bivariate analysis, predictors of poor outcome were any signs of mass effect on imaging, clinical deterioration after admission, and age. In contrast, clinical symptoms on admission and parenchymal lesions per se, such as edema, infarction, or hemorrhage were not predictive. Multivariate predictors of poor outcome were an increase in National Institutes of Health Stroke Scale ≥3 after admission [odds ratio (OR) 6.7], bilateral motor signs in the further course (OR 9.2), and midline shift (OR 5.1).

Conclusion

The outcome of severe CVT is almost equally divided between severe impairment or death and survival with no or only mild handicap. Specifically, space-occupying mass effect and associated neurologic deterioration seem to determine a poor outcome. Therefore, early detection and treatment of mass effect should be the focus of critical care.

     

Cement leakage as a possible complication of balloon kyphoplasty—is there a difference between osteoporotic compression fractures (AO type A1) and incomplete burst fractures (AO type A3.1)?

Background  

Besides the treatment of osteoporotic vertebral compression fractures of AO type A1, balloon kyphoplasty (BKP) is seen as a therapeutic option even in the treatment of incomplete osteoporotic burst fractures (AO type A3.1). However, due to involvement of the posterior vertebral body wall, the risk of cement leakages is considered to be higher. This study focuses on the frequency and pattern of cement leakages in AO type A3.1 fractures compared with osteoporotic compression fractures (AO type A1).     

Pathologie und Therapie der Rotatorenmanschettenl?sion

The differentiation between traumatic and degenerative rotator cuff lesions is of high importance in everyday clinical practice. Knowledge of the anatomy and biomechanics are essential for the treatment of patients. In the past 15?years, increasing knowledge of the biomechanics of the shoulder joint and surgical treatment options, particularly in arthroscopic reconstructive options, has evolved. Full documentation of primary clinical findings and the close-knit follow-up documentation are of the utmost importance for an expert evaluation. The authors summarize the key aspects of treatment and possible therapeutic options of rotator cuff lesions.     

Total intravenöse Anästhesie mit Propofol und Remifentanil

INTRODUCTION: The aim of this study was to investigate efficacy and tolerability of propofol, remifentanil and cisatracurium or mivacurium in routine anesthetic practice. PATIENTS AND METHODS: A total of 6,161 patients scheduled for abdominal or orthopedic surgery were included in this open multicenter phase IV study. Perioperative hemodynamics as well as induction, recovery and discharge times, anesthetics, frequency of PONV and side-effects were studied. RESULTS: Quality of induction and maintenance of anesthesia were evaluated by anesthesiologists to be good or very good in 88%. 86% of the patients assessed anesthesia as good or very good. Adverse events were reported for 28 patients (0.45%), with hypotension and bradycardia being most frequent. Recovery was evaluated by anesthesiologists to be good or very good in 88%, surgeons and nursing staff assessed the TIVA as good or very good in 90%. Most frequent postoperative complaints were pain (16.7%), nausea (6.1%), shivering (3.1%) and vomiting (0.7%). CONCLUSIONS: The study showed that total intravenous anesthesia using propofol, remifentanil and cisatracurium or mivacurium is safe, tolerable and effective and has a high degree of acceptance.     

A randomised controlled trial of intravenous dexmedetomidine added to dexamethasone for arthroscopic rotator cuff repair and duration of interscalene block

Prolongation of peripheral nerve blockade by intravenous dexamethasone may be extended by intravenous dexmedetomidine. We randomly allocated 122 participants who had intravenous dexamethasone 0.15 mg.kg⁻¹ before interscalene brachial plexus block for day-case arthroscopic rotator cuff repair to intravenous saline (62 participants) or intravenous dexmedetomidine 1 μg.kg⁻¹ (60 participants). The primary outcome was time from block to first oral morphine intake during the first 48 postoperative hours. Fifty-nine participants reported taking oral morphine, 25/62 after placebo and 34/60 after dexmedetomidine, p = 0.10. The time to morphine intake was shorter after dexmedetomidine, hazard ratio (95%CI) 1.68 (1.00–2.82), p = 0.049. Median (IQR [range]) morphine doses were 0 (0–12.5 [0–50]) mg after control vs. 10 (0–30 [0–50]) after dexmedetomidine, a difference (95%CI) of 7 (0–10) mg, p = 0.056. There was no effect of dexmedetomidine on pain at rest or on movement. Intra-operative hypotension was recorded for 27/62 and 50/60 participants after placebo vs. dexmedetomidine, respectively, p < 0.001. Other outcomes were similar, including durations of sensory and motor block. In conclusion, dexmedetomidine shortened the time to oral morphine consumption after interscalene block combined with dexamethasone and caused intra-operative hypotension.     

Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute-phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF-alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis.     

Prognosis of patients with acute renal failure requiring dialysis: results of a multicenter study

Despite several decades of clinical experience, the mortality rate for patients with acute renal failure (ARF) requiring dialysis remains high, and the evaluation of the patients prognosis has been difficult. To date, the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system has been used more frequently for prediction in studies of ARF than any other scoring system, but has not been prospectively validated in controlled multicenter studies of this entity. In a multicenter, prospective, controlled trial evaluating the use of biocompatible hemodialysis membranes (BCMs) in patients with ARF, we evaluated the extent to which the APACHE II scoring system, based on the physiological variables in the 24 hours before the onset of dialysis and the presence or absence of oliguria, is predictive of outcome. Analysis of survival and recovery of renal function for the 153 patients treated in this study show that APACHE II scores are predictive both of survival and recovery of renal function, whether analyzed separately by type of dialysis membrane used (BCM or bioincompatible [BICM]) or for both groups combined (all P < 0.01). There was no evidence of a significant center effect or interaction of APACHE II score with dialysis membrane in our study. After adjusting for the APACHE II score, there was a positive effect of the BCM on both probability of survival (P < 0.05) and recovery of renal function (P < 0.01). In patients dialyzed with BCMs, oliguria at onset of dialysis had an adverse effect on both survival and recovery of renal function (both P < 0.01). Receiver operator curves (ROCs) using APACHE II score and the use of BCMs in nonoliguric patients yielded a statistically significant improvement versus the use of APACHE II score alone in the area under the curve (AUC) for survival (0.747 to 0.801; P < 0.05) and recovery of renal function (0.712 to 0.775; P < 0.05). We conclude that the use of the APACHE II score determined at the time of initiation of dialysis for patients with ARF is a statistically significant predictor of patient survival and recovery of renal function. The use of the APACHE II score measured at the time of dialysis initiation, especially when modified by the presence or absence of oliguria, should help in predicting outcome when evaluating interventions for patients with ARF.     

The efficacy of dietary intervention on urinary risk factors for stone formation in recurrent calcium oxalate stone patients

PURPOSE: Nutrition is suggested to be the major environmental risk factor in idiopathic calcium oxalate stone disease. The study was designed to evaluate the effect of dietary intervention on urinary risk factors for recurrence in calcium oxalate stone formers. MATERIALS AND METHODS: A total of 76 men and 31 women with idiopathic calcium oxalate stone disease collected 24-hour urine on their habitual, self-selected diets and after 7 days on a balanced standardized diet according to the recommendations for calcium oxalate stone formers. RESULTS: On the usual diet, a urine volume of less than 2.0 l per 24 hours was present in 57.9%, hypercalciuria in 25.2%, hypomagnesuria in 18.7%, hyperoxaluria in 14.0%, hyperuricosuria in 41.3% and hypocitraturia in 57.0% of patients. The frequency of metabolic abnormalities and the risk of calcium oxalate stone formation decreased significantly on the ingestion of the balanced diet, due to the significant increase in urinary volume, pH and citrate excretion and the significant decrease in urinary calcium and uric acid excretion. No change occurred in urinary oxalate and magnesium excretion. CONCLUSIONS: The evaluation of urinary risk profiles of the patients on their usual dietary habits revealed a high risk for calcium oxalate stone formation. A low fluid intake and an increased intake of protein and alcohol were identified as the most important dietary risk factors. The shift to a nutritionally balanced diet according to the recommendations for calcium oxalate stone formers significantly reduced the stone forming potential.     

Intraoperative low-dose S-ketamine has no preventive effects on postoperative pain and morphine consumption after major urological surgery in children

BACKGROUND: Clinical studies suggest low-dose ketamine may have preemptive effects on postoperative pain in adults. The objective of this study was to determine whether intraoperative low-dose S-ketamine reduces postoperative pain and morphine consumption in children undergoing major urological surgery. MATERIALS: Thirty children scheduled for major urological surgery were included in this prospective study. Anesthesia was performed as total intravenous anesthesia (TIVA) with alfentanil and propofol. Fifteen patients additionally received an intravenous bolus of S-ketamine (0.2 mg.kg-1) followed by a continuous infusion of 5 microg.kg-1.min-1, which was stopped immediately after skin closure (Ketamine Group). Another 15 patients received an infusion of saline (Control group). After transfer to the PACU, pain intensity was evaluated using a numeric rating scale (NRS). First patient controlled analgesia (PCA) request, cumulative morphine consumption and pain intensities within the first 72 h were compared. RESULTS: Morphine consumption was not significantly different during the first 72 h (Control: 0.4 mg.kg-1, 0.24-0.51 mg.kg-1, Ketamine: 0.32 mg.kg-1, 0.19-0.61 mg.kg-1; median, 25-75% percentile; n.s.). However, differences were found in pain intensity during the first postoperative hour (Control: 4.0, 3.2-4.6, Ketamine: 2.5, 1.3-3.5; median, 25-75% percentile; P<0.05) and in the time to first PCA use (Control: 37, 28-46 min, Ketamine: 62, 38-68 min; median, 25-75% percentile; P<0.05). CONCLUSIONS: Intraoperative low-dose S-ketamine had no effect on morphine consumption during the first 72 h after surgery. The differences in pain intensity and time to first PCA use probably reflect additional sedation and antinociceptive effects of S-ketamine rather than a true 'prevention' of pain.