Geographic regional differences in rocuronium bromide dose-response relation and time course of action: an overlooked factor in determining recommended dosage.

BACKGROUND: Geographic location is not acknowledged as a stratifying factor that can directly affect drug potency, because drugs are still licensed with the same recommended dose for different geographic regions. The aim of the current study was to compare the potency and duration of action of rocuronium bromide in 54 patients in three countries with different life habits, diet, and ambient conditions, namely white Austrians, white North Americans, and Han Chinese in China. METHODS: Neuromuscular block of six consecutive 50-microg/kg rocuronium incremental doses followed by 300 microg/kg was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, Holland). Dose-response curves were created using log-dose-probit transformation. The authors compared rocuronium bromide ED50, ED90, and ED95 (effective doses required for 50%, 90%, and 95% first twitch depression, respectively) as well as Dur25 and Dur0.8 (times from last incremental dose administration until 25% first twitch and 0.8 train-of-four ratio recovery, respectively) in patients of the three countries. RESULTS: Rocuronium ED50, ED90, and ED95 were significantly higher in Austrian patients (258 +/- 68, 530 +/- 159, and 598 +/- 189 microg/kg) and Chinese patients (201 +/- 59, 413 +/- 107, and 475 +/- 155 microg/kg) compared with American patients (148 +/- 48, 316 +/- 116, and 362 +/- 149 microg/kg, respectively). Dur25 and Dur0.8 were significantly shorter in Austrian patients (22.3 +/- 5.5 and 36.9 +/- 12.8 min) and Chinese patients (30.4 +/- 7.5 and 45.7 +/- 15.9 min) compared with American patients (36.7 +/- 8.5 and 56.2 +/- 16.7 min, respectively). CONCLUSIONS: The authors demonstrated a significant difference in rocuronium potency and duration of action among patients in the three countries. Larger studies are required for determining dosage recommendations for different geographic regions.

Remifentanil versus morphine analgesia and sedation for mechanically ventilated critically ill patients: a randomized double blind study.

BACKGROUND: The rapid onset and offset of action of remifentanil could make it quickly adjustable to the required level of sedation in critically ill patients. The authors hypothesized that the efficacy of a remifentanil-based regimen was greater than that of a morphine-based regimen. METHODS: Forty intent-to-treat patients were randomly allocated to receive a blinded infusion of either remifentanil 0.15 microg x kg(-1) x min(-1) or morphine 0.75 microg x kg(-1) x min(-1). The opioid infusion was titrated, in the first intent, to achieve optimal sedation defined as Sedation Agitation scale of 4. A midazolam open-label infusion was started if additional sedation was required. RESULTS: The mean percentage hours of optimal sedation was significantly longer in the remifentanil group (78.3 +/- 6.2) than in the morphine group (66.5 +/- 8.5). This was achieved with less frequent infusion rate adjustments (0.34 +/- 0.25 changes/h) than in the morphine group (0.42 +/- 0.22 changes/h). The mean duration of mechanical ventilation and extubation time were significantly longer in the morphine group (18.1 +/- 3.4 h, 73 +/- 7 min) than in the remifentanil group (14.1 +/- 2.8 h, 17 +/- 6 min), respectively. Remifentanil mean infusion rate was 0.13 +/- 0.03 microg x kg(-1) x min(-1), whereas morphine mean infusion rate was 0.68 +/- 0.28 microg x kg(-1) x min(-1). More subjects in the morphine group (9 of 20) than in the remifentanil group (6 of 20) required midazolam. The incidence of adverse events was low and comparable across the two treatment groups. CONCLUSIONS: A remifentanil-based regimen was more effective in the provision of optimal analgesia-sedation than a standard morphine-based regimen. The remifentanil-based regimen allowed a more rapid emergence from sedation and facilitated earlier extubation.

The effect of different stages of neuromuscular block on the bispectral index and the bispectral index-XP under remifentanil/propofol anesthesia.

Facial electromyographic activity and neuromuscular block could influence bispectral index (BIS) depth of anesthesia monitoring. In this study we examined, in 30 patients undergoing general surgical procedures, the effect of different stages of neuromuscular block on BIS monitoring and compared the conventional A-2000 BIS trade mark (BIS(3.4)) with the new BIS-XP trade mark (BIS(XP)). At deep surgical anesthesia BIS(3.4) of approximately 40, under a propofol 3.61 microg/mL target-controlled infusion and a 0.15-0.3 microg. kg(-1). min(-1) remifentanil infusion, mivacurium 0.15 mg/kg was administered. The onset of neuromuscular block triggered a brief transient odd divergence in response that manifested as a BIS(3.4) increase from 43 +/- 4 to 49 +/- 7 (P = 0.007) and a BIS(XP) decline from 41 +/- 3 to 35 +/- 3 (P = 0.003) at 1 +/- 0.2 min. Then, 2.5 +/- 1 min after mivacurium administration, both monitors returned to baseline values of 43 +/- 5 and 40 +/- 4, respectively. After that, BIS(3.4) and BIS(XP) did not significantly change during complete neuromuscular block or during various levels of neuromuscular recovery. At all phases, BIS(XP) was significantly lower than BIS(3.4). Our study indicated that the BIS(3.4)/BIS(XP) bias and the wide limits of agreement do not allow values given by the two monitors to be used interchangeably.

Procalcitonin and C-reactive protein plasma concentrations in nonseptic uremic patients undergoing hemodialysis.

OBJECTIVE: To assess procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations and clearance in nonseptic end-stage renal failure patients undergoing their first three hemodialysis sessions. DESIGN AND SETTING: Prospective observational consecutive clinical study at a university hospital. PATIENTS: The study recruited 55 end-stage renal failure patients without evidence of systemic infection undergoing the creation of an arteriovenous fistula to start hemodialysis for the first time. INTERVENTIONS: Blood samples were collected before and after each of the first three (4-5 h) hemodialysis sessions. PCT was assayed by immunoluminometry. MEASUREMENTS AND RESULTS: The mean plasma concentration of PCT prior to the first three hemodialysis sessions declined significantly following each session. There was no significant difference between CRP plasma concentrations before and after hemodialysis sessions. CONCLUSIONS: The presence of an elevated PCT in plasma of not yet dialyzed uremic nonseptic patients indicates that uremia per se and not the dialysis process is the origin of such elevation. PCT levels declined with successive hemodialysis sessions. We propose that in the not yet dialyzed uremic nonseptic patients a baseline PCT level of approx. 1.5 ng/ml should be expected. Although the mean plasma CRP level was elevated, hemodialysis had no significant effect on CRP concentration, making CRP a possible useful marker of sepsis in these patients.

Side-effects after inhalational anaesthesia for paediatric cerebral magnetic resonance imaging.

BACKGROUND: The aim of this study was to evaluate the type, incidence and duration of postprocedure side-effects in 168 children within the first 72 h after inhalational anaesthesia for magnetic resonance imaging (MRI). METHODS: Premedication and induction followed standardized routines. Maintenance of anaesthesia was performed with inhalational anaesthetics solely: isoflurane (n=60 of 112; 53%), sevoflurane (n=32 of 112; 29%), desflurane (n=12 of 112; 11%) or halothane (n= 8 of 112; 7%) using a strapped on face mask (FiO2=0.4; flow 5 l.min-1). When indicated, gadolinium was administered (n=45; OF 112; 40%). RESULTS: One hundred and twelve of 168 parents (67%) responded to questionnaires. In these 112 children, pathological MR findings were found supratentorially (n=31; 28%), infratentorially (n=9; 8%), extracerebrally (n=12; 11%) or combined (n=9; 8%). In 56 of these 112 children (50%), 14 different side-effects were reported. One hour after anaesthesia, 55 children suffered between one and four side-effects. Neurological side-effects were associated with age > or = 5 years (P < 0.01) or infratentorial pathophysiology (P < 0.01) and abdominal side-effects (P < 0.02), especially nausea (P < 0.001) with age > or = 5 years. CONCLUSIONS: Our findings indicate the need to inform parents of the incidence and variability of side-effects after inhalational anaesthesia for minimally invasive, diagnostic procedures, such as MRI.

End-stage renal failure reduces central clearance and prolongs the elimination half life of remifentanil.

PURPOSE: To evaluate the pharmacokinetics of remifentanil in 13 end-stage renal failure patients compared to matched control patients with normal renal function. METHODS: Remifentanil was infused for 20 min at a rate of 0.1 microg x kg(-1) x min(-1). Serial arterial blood samples (3 mL) were drawn at the start of infusion (zero), five, ten, 15, 20, 22.5, 25, 27.5, 30, 35, 40, 45, 50, 55 and 60 min. Blood samples were immediately preserved with citric acid and chilled on ice. High performance liquid chromatography-tandem mass spectrometry concentration assay was performed using GI 95779B internal standard. RESULTS: A two-compartment pharmacokinetic model provided an adequate fit for individual patient data. There was no difference in the mean +/- SD distribution half life (t1/2) between the renal failure group (1.65 +/- 0.7 min) and the control group (1.58 +/- 0.54 min). There was a significant difference in the central clearance (Cl(c)) and elimination half life (t1/2) ss) between the renal failure group (28 +/- 7 mL x kg(-1) x min(-1) and 18.86 +/- 2.06 min, respectively) and the control group (46.3 +/- 13.8 mL x kg(-1) x min(-1) and 16.35 +/- 2.99 min, respectively). Remifentanil blood concentrations were significantly higher in the renal failure group than in the control group. CONCLUSION: We have demonstrated a significant reduction in the Cl(c) and a prolongation of t1/2 ss of remifentanil in end-stage renal failure patients. While statistically significant, these variations in the pharmacokinetics of remifentanil were clinically modest and may be explained by a reduced volume of distribution in the period following hemodialysis.

The neuromuscular transmission module versus the relaxometer mechanomyograph for neuromuscular block monitoring.

UNLABELLED: The neuromuscular transmission module (M-NMT) is an integrated piezoelectric motion sensor module incorporated in the AS/3(TM) anesthesia monitor. We compared the neuromuscular block of 0.6 mg/kg rocuronium (twice the 95% effective dose) monitored by the M-NMT with that monitored by the Relaxometer mechanomyograph (MMG). The two monitors were alternately allocated to the left or right hands of 20 patients. T(1)%, the first twitch of the train-of-four (TOF), and the TOF ratio (T(4)/T(1)) were used for evaluating the neuromuscular block. There was no significant difference in the mean (min) plus minus SD onset time or time to 0.8 TOF ratio recovery measured by the M-NMT (1.5 plus/minus 0.3, 49.4 plus/minus 8.1) compared with MMG (1.8 plus/minus 0.6, 50.9 plus/minus 9.9), respectively. However, the time (min) to 25% T(1) recovery was significantly longer when monitored by the M-NMT (25.6 plus/minus 8) than by the MMG (20.2 plus/minus 6.3). During recovery from neuromuscular block, the difference between the TOF ratios measured by the two monitors showed a bias of -0.031, and the limits of agreement (bias plus/minus 1.96 SD) were -0.281 and +0.22. The M-NMT monitor could determine the time to tracheal intubation as well as full recovery from neuromuscular block, but it lagged behind the MMG in determining the time to rocuronium repeat dose administration. IMPLICATIONS: Compared with the Relaxometer mechanomyograph, the neuromuscular transmission module could equally indicate time to tracheal intubation and full recovery from 0.6 mg/kg rocuronium neuromuscular block. Its small quick-fit sensor has the advantage, in an often crowded and busy operating room, of being incorporated in the AS/3(TM) anesthesia workstation.