Effect-site concentration of remifentanil for laryngeal mask airway insertion during target-controlled infusion of propofol

The purpose of this study was to determine the effect-site concentration of remifentanil that would provide optimal conditions for successful laryngeal mask airway insertion during a target-controlled infusion (TCI) of propofol at 3.5 μg.ml⁻¹ without the use of neuromuscular blockade. Five minutes after propofol infusion, remifentanil was infused at a dose determined by a modified Dixon's up-and-down method. Five minutes after remifentanil infusion, the laryngeal mask was inserted. The effect-site concentration of remifentanil for successful laryngeal mask insertion in 50% of adults (EC₅₀) was 3.04 (SD 0.49) ng.ml⁻¹ during a TCI of 3.5 μg.ml⁻¹ propofol without neuromuscular blockade. From the probit analysis, the EC₅₀ and EC₉₅ of remifentanil were 2.84 ng.ml⁻¹ (95% CI 2.09–3.57 ng.ml⁻¹) and 3.79 ng.ml⁻¹ (95% CI 3.26–9.25 ng.ml⁻¹), respectively.     

The influence of sperm/zona pellucida collision rates on zona binding

Summary. The satisfying success rates reported with intra-cytoplasmic sperm injection (ICSI) urged clinicians and scientists to re-address the emphasis in the management of the male factor patient towards gamete manipulation in order to circumvent the underlying problem causing fertilization failure. We have designed a study to (i) calculate the collision rate of a sperm population with the human zona pellucida, using a mathematical hypothesis and (ii) use the calculated collision rate to evaluate subsequent zona binding results obtained under hemizona assay conditions. Microdroplets were used to co-incubate sperm and human oocytes in order to evaluate zona binding. Using microvolumes, the track followed by sperm, as well as the maximum distance travelled were employed to calculate the collision rate of sperm and zona pellucida. The sperm concentrations of swim up samples were adjusted to 4 × 10⁶ and 0.8 × 10⁶ sperm ml⁻¹. Five separate droplets each of 20 μl containing 4 × 10⁶ sperm ml⁻¹ (80000 motile sperm) and 200 μl containing 0.8 × 10⁶ sperm ml⁻¹ (160000 motile sperm), respectively, were prepared. Both volumes were incubated for 18 h at 37°C. The mean (±SD) number of spermatozoa tightly bound to hemizona, incubated in 20 μl and 200 μl sperm droplets, was 2444±612 and 548±315, respectively ( P = 0.0001). The results can be used as a guideline to calculate the optimum insemination concentration needed for a specific sperm population to ensure the maximum collision rates with the oocyte.     

Scavenging effect of N-acetyl-L-cysteine against reactive oxygen species in human semen: a possible therapeutic modality for male factor infertility?

Summary. A new approach to reduce the level of reactive oxygen species (ROS) in human semen by using N-acetyl-L-cysteine (NAG) was evaluated. Semen samples were incubated with or without NAC (1.0 nig ml⁻¹) at room temperature. The chemiluminescent signal of the oxidation of luminol was detected by means of an MTP reader after 0, 20, 40, 60 and 120 min, respectively, using 200 μM luminol. In addition, the dose-dependent action of NAC (0.1, 1.0 and 5.0 mg ml⁻¹) and the influence of NAC on functional sperm parameters (motility and acrosome reaction) were studied.
ROS levels decreased significantly after 20 min incubation with NAG. This reduction was greater in the high ROS group (>30 000 counts/10⁷ viable sperm at t = 0) than in the low ROS group (<30 000). In addition, a marked dose-dependence of NAC was observed. Concerning sperm function, total sperm motility improved after incubation with NAC, but no significant change was observed with respect to the acrosome reaction.
NAC (at concentrations of 1.0 mg ml⁻¹) significantly reduced ROS in human semen and showed the possibility of improving impaired sperm function. After further testing NAC might be useful for the treatment of male infertility patients.     

The relationship between ejaculated ram sperm mitochondrial protein synthesis and motility

Summary. D-chloramphenicol, at concentrations of 20 and 40 μg/ml, inhibited over 80% of the newly synthesized mitochondrial proteins expressed by incorporation of ³H-amino acid mixture. At concentrations of 20 and 40 μgml⁻¹, D-chloramphenicol enhanced the collective motility of washed ram spermatozoa. The collective motility measured by the multichannel Reflectospermiograph system, significantly enhanced the motility wave frequencies and amplitudes by 24–17% and 65–32%, respectively. Furthermore, the longevity of the collective motility was prolonged by 12–19%. In about 20% of the cases, when the original sperm motility was low, it was found that 40 μg ml⁻¹ D-chloramphenicol has maximum stimulation effect on sperm motility in inverse fashion. Since the mitochondria are located adjacent to the motility initiation area, it can be speculated that the mitochondrial protein(s) directly inhibiting the axonemal-ATPase activity or indirectly blocking sperm metabolite, are essential for maintaining sperm motility.     

Effects of propofol emulsion and thiopentone on T helper cell type-1/type-2 balance in vitro

We have earlier found increased percentages of T helper cells (CD4-positive lymphocytes) in the blood circulation after propofol infusion anaesthesia. Cytokines interferon-γ (IFNγ) and interleukin-4 (IL-4) are important in the differentiation of T helper cells into subtypes T helper type-1 (Th1) and type-2 (Th2). To study the effects of propofol emulsion, its solvent Intralipid^® and thiopentone on Th1/Th2 balance, measurements of IFNγ and IL-4 production by mononuclear leucocytes were carried out in vitro . As IL-2 has a central role in immune responses to surgery, its production was also measured. Concanavalin A-stimulated mononuclear cells were cultured in the presence of propofol emulsion at 3.5 or 10 μg.ml⁻¹, Intralipid^® 35 or 100 μg.ml⁻¹, or thiopentone 3 μg.ml⁻¹. Cytokine production was measured from the conditioned media of mononuclear cell cultures. Decreased IFNγ (p <0.001) and IL-4 concentrations (p < 0.01) were found in the presence of thiopentone, but IL-2 production was unaffected. By contrast, propofol emulsion or Intralipid^® had no effects on IFNγ, IL-2 or IL-4 concentrations. Propofol 10 μ.ml⁻¹ increased the IFNγ/IL-4 ratio from the control value median 243 (162–562) (25th–75th percentile) to 363 (195–1028) (p < 0.01), but thiopentone decreased it to 145 (60–214) (p < 0.01). These findings show that propofol and thiopentone have different effects in vitro on Th1/Th2 balance and suggest that they have different modulating effects on the immune response.     

Influence of different uropathogenic microorganisms on human sperm motility parameters in an in vitro experiment

Summary. The influence of different uropathogenic microorganisms ( E. coli, enterococcus, Pseudomonas aeruginosa, Staphylococcus saprophyticus, Candida albicans ) on human sperm motility was studied in vitro with a computer-assisted sperm analyser (CASA).
Native ejaculates were prepared with the swim-up technique and adjusted to 22 times 10⁶ spermatozoa ml⁻¹. The sperm suspension was artificially infected with microorganisms in concentrations varying from 2 times 10³ to 2 times 10⁷. Sperm motility was examined directly after incubation, 2, 4 and 6 h later using the Mika motion analysis®, a computer-based, automatic motility analysis.
Former results with E. coli (serotype 06) could be confirmed that a significant inhibitory effect on sperm motility was associated with bacterial growth. Experiments with the enterococcus strain and Staphylococcus saprophyticus indicated no significant influence on sperm motility parameters. Tests with Pseudomonas aeruginosa showed a decrease of progressive motility according to time, but not to different bacterial concentrations. A significant inhibitory effect of Candida albicans was only detected in the samples with the initial bacterial concentration of 2 times 10⁷ microorganisms ml⁻¹.     

Pulmonary function and inflammatory markers in patients undergoing coronary revascularisation with or without cardiopulmonary bypass

Lung injury after cardiac surgery is believed to result from cardiopulmonary bypass and its pro-inflammatory effects. To test this hypothesis, we compared the oxygenation ratios, extravascular lung water indices and systemic and pulmonary tumour necrosis factor alpha (TNF-α) and interleukin (IL)-8 at predetermined intervals in coronary artery surgery patients with or without cardiopulmonary bypass. No differences in oxygenation ratios or extravascular lung water indices were found. Serum values of TNF-α and IL-8 increased in both groups but were higher in the cardiopulmonary bypass group (end of surgery: mean (SD) TNF-α 3.68 (2.5) vs 2.20 (1.2) pg.ml⁻¹ (p  =  0.043 (CI 0.05–2.9)) and mean (SD) IL-8 19.45 (10.8) vs 6.31 (5.3) pg.ml⁻¹ (p  =  0.001 (CI 6.9–19.3)). In broncho-alveolar lavage fluid, TNF-α and IL-8 increased in both groups with no differences between the groups.     

Single injection paravertebral block for renal surgery in children

Background:  Continuous paravertebral block (PVB) has been successfully used for postoperative analgesia in children. However, data regarding the efficacy of a single injection technique for major renal surgery are still lacking.
Methods:  Following the ethics committee approval and parent informed consent, 24 children (median 10.3 months; range: 2.9–26.8) undergoing major renal surgery were included in a prospective observational pilot study. Following a standardized general anesthetic the patients were administered a single injection low thoracic PVB (loss-of-resistance technique; 0.5 ml·kg⁻¹ of levobupivacaine 2.5 mg·ml⁻¹ with epinephrine 5 μg·ml⁻¹) at the end of surgery. Postoperative pain was assessed by Face, Legs, Activity, Cry, Consolability (FLACC) score at predetermined time points and in case of apparent patients' discomfort during the first 12 postoperative hours. The duration of postoperative analgesia was defined as the interval between PVB and the first supplemental administration of a rescue opioid analgesic. The incidence of complications and postoperative vomiting (POV) was also recorded.
Results:  A successful PVB was achieved in 23/24 patients (95.8%). The median duration of the block was 600 min (range: 180–720 min) with 10 children not requiring any supplemental analgesia during the 12-h observation period. Vascular puncture was observed in 2/24 children (8.3%) and POV occurred in 4/24 children (16.7%). All complications were considered minor and did not influence recovery.
Conclusions:  Single injection PVB provided clinically relevant postoperative analgesia in children undergoing major renal surgery.     

Predictors of improved seminal characteristics by varicocele repair

The aim of this study was to investigate predictors of the improvement of semen characteristics after low ligation for patients with varicoceles. The records of 97 oligozoospermic patients who underwent microsurgical left or bilateral inguinal varicocele repair were retrospectively evaluated. We assessed factors that could be predictors of the improvement of semen characteristics using logistic regression analysis. We evaluated age, testicular volume, varicocele grade, serum follicle-stimulating hormone (FSH), luteinising hormone, testosterone, sperm concentration and motility before low ligation. Among the 97 patients, sperm concentration improved from 6.4 ± 5.8 to 24.2 ± 35.1 million ml⁻¹ and sperm motility increased from 32.8 ± 24.9% to 41.0 ± 14.6% in 55 patients (57%). In logistic regression analysis, pre-operative serum FSH and testosterone concentration were predictors of sperm concentration improvement. Varicocele repair improved sperm concentration and motility. Low serum FSH and high testosterone are significant factors predicting the improvement of semen characteristics before low ligation.     

A comparison of volatile and non volatile agents for cardioprotection during on-pump coronary surgery

A randomised study of 414 patients undergoing coronary artery surgery with cardiopulmonary bypass was conducted to compare the effects of a volatile anaesthetic regimen with either deesflurane or sevoflurane, and a total intravenous anaesthesia (TIVA) regimen on postoperative troponin T release. The primary outcome variable was postoperative troponin T release, secondary outcome variables were hospital length of stay and 1-year mortality. Maximal postoperative troponin T values did not differ between groups (TIVA: 0.30 [0.00–4.79] ng.ml⁻¹ (median [range]), sevoflurane: 0.33 [0.02–3.68] ng.ml⁻¹, and desflurane: 0.39 [0.08–3.74] ng.ml⁻¹). The independent predictors of hospital length of stay were the EuroSCORE (p < 0.001), female gender (p = 0.042) and the group assignment (p < 0.001). The one-year mortality was 12.3% in the TIVA group, 3.3% in the sevoflurane group, and 6.7% in the desflurane group. The EuroSCORE (p = 0.003) was the only significant independent predictor of 1-year mortality.     

Use of a novel non-steroidal anti-inflammatory drug, nimesulide, in the treatment of abacterial prostatovesiculitis

Summary. Nimesulide, a novel non-steroidal anti-inflammatory drug, was used in cases of abacterial prostato-vesiculitis. Thirty patients with a mean age of 33.7 years (range 18–58) were studied. Nimesulide was administered orally 100 mg b.i.d. for three cycles of 10 d each. Dysuric symptoms, semen analysis, and transrectal ultrasound were examined during the study. The concentration-time curves of nimesulide (NIM) and its metabolite, hydroxynimesulide (OH-NIM) in seminal fluid were also evaluated after single oral administration (100 mg) using an HPLC technique. Following administration of the drug, the Cmax was reached in seminal fluid at the second hour for NIM (with a mean value ± SD of 0.58 ± 0.13 μg ml⁻¹) and at the fourth hour for OH-NIM (2.98 ± 0.38 μg ml⁻¹). Maximal seminal fluid concentrations compared to blood plasma levels were observed at the fourth hour for both substances (31.73 ± 2.34% for NIM; 31.87 ± 8.66% for OH-NIM.
Dysurie symptoms were relieved in 20 (66%) patients. A clear amelioration of inflammatory signs were observed at transrectal ultrasound evaluation in 16 (54%) patients. No statistically significant changes of sperm count and motility in the whole sample were observed, while a significant reduction in the number of abnormal forms occurred. From these results, nimesulide appears to be an effective anti-inflammatory drug with a good diffusion into the genital apparatus and low side-effects.     

Plasma bupivacaine levels after fascia iliaca compartment block with and without adrenaline

Twenty children undergoing unilateral surgery on the thigh received a fascia iliaca compartment block using 2 mg·kg⁻¹ of bupivacaine with (Group A) or without (Group P) adrenaline 1/200 000. Venous blood samples were taken as 5, 10, 15, 20, 25, 30, 40, 50 and 60 min after injection and assayed for concentrations of bupivacaine. In all subjects an adequate block was produced. Plasma concentrations of bupivacaine in Group P were significantly higher than those in Group A ( P <0.05). The median maximum plasma concentration (C_max) was 1.1 μg·ml⁻¹ (range 0.54–1.29 μg·ml⁻¹) in Group P and 0.35 μg·ml⁻¹ (range 0.17–0.96 μg·ml⁻¹) in Group A. The median time taken to attain C_max (T_max) was 20 min (range 10–25 min) in Group P and 45 min (range 5–50 min) in Group A. The median time to first analgesia was 9.75 h (range 3–15 h) in Group P and 10.5 h (range 2.5–21 h) in Group A. The study confirmed the efficacy of the fascia iliaca compartment block in children and showed that when performed with 2 mg·kg⁻¹ of bupivacaine it is associated with plasma concentrations of bupivacaine well within acceptable limits. The addition of adrenaline 1/200 000 to the local anaesthetic solution reduces the maximum plasma concentration reached.     

Seminal fibronectin-like antigen and transferrin concentrations in infertile and fertile men

Summary.  Fibronectin like antigen (Fn) and transferrin (Trs) levels were measured in the seminal plasma of 40 fertile and 102 infertile men. The concentrations of both proteins were significantly ( P <0.001) higher in the fertile controls compared to the infertile groups. The levels of Fn and Trs (mean value ± SEM) in the fertile men were 857.9 ± 9.8 μg ml^-1 and 164.0 ± 6.5 μg ml^-1, respectively; in the azoospermic men ( n = 17) 552.7 ± 24.65 μg ml^-1 and 20.7 ± 2.19 μg ml^-1, respectively; in the group of severe oligozoospermia ( n = 35) 568.34 ± 25.7 μg ml^-1 and 31.1 ± 4.18 μg ml^-1, respectively; in the moderate oligozoospermic group ( n = 8) 572.50 ± 47.9 μg ml^-1 and 43.4 ± 15.4 μg ml^-1 respectively, and in the asthenozoospermic group ( n = 26) 512.76 ± 40.4 μg ml^-1 and 47.0 ± 7.9 μg ml^-1, respectively. Of special interest was the finding from a group of 16 normospermic men (partners of couples with unexplained infertility) who showed significantly lower levels of Fn like antigen, 632.5 ± 26.9 μg ml^-1 ( P <0.001) and Trs 41.8 ± 6.94 μg ml^-1 ( P <0.0001) compared to normals. No correlation was found between Fn levels with either Trs or FSH levels or sperm count. In conclusion, our results indicate that male infertility is associated with changes in seminal plasma Fn like antigen concentrations and that it can be possibly used as an index of sperm fertilizing capacity.     

Gonadal and Extragonadal Sperm Reserves of the Brazilian Nelore Zebu (Bos indicus)

Summary: Gonadal and extragonadal sperm reserves were estimated through hemocytometric method in six Nelore zebu bulls, aging 4–6 years, with normal spermatogenesis, and kept at sexual rest. Gonadal sperm reserve was estimated to be 47.8 ± 5.8 times 10⁶ sperm cells/g testis parenchyma and 9.8 ± 1.7 times 10⁹ sperm cells/testis. Using a time divisor of 4.94 days the daily sperm production was estimated to be 10.0 ± 0.9 times 10⁶ sperm cells/g testis parenchyma/day and 2.0 ± 0.3 times 10⁹ sperm cells/testis/day. Epididymal sperm reserve amounted 11.9 ± 1.6 times 10⁹ spermatozoa/organ, distributed as follows: 35.3 ± 3.6% in the head, 16.9 ± 1.7% in the body and 47.7 ± 3.7% in the tail.
Zusammenfassung: Gonadale und extragonadale Spermareserven des brasilianischen Nelore-Zebu (Bos indicus)
Bei sechs Nelore-Zebubullen im Alter von vier bis sechs Jahren mit normaler Spermatogenese und unter sexueller Karenz wurden mit einer haemocytometrischen Methode die gonadalen und extragonadalen Spermareserven bestimmt. Für die gonadale Spermareserve wurden Werte von 47.8 ± 5.8 times 10⁶ Spermatozoen/g Hodenparenchym und 9.8 ± 1.7 times 10⁹ Spermatozoen/Hoden gefunden. Unter Benutzung eines Zeitdivisors von 4.94 Tagen berechnet sich die tägliche Spermaproduktion zu 10.0 ± 0.9 times 10⁶ Spermatozoen/g Hodenparenchym/Tag und 2.0 ± 0.3 times 10⁹ Spermatozoen/Hoden/Tag. Die Spermareserve im Nebenhoden betrug 11.9 ± 1.6 times 10⁹ Spermatozoen/Nebenhoden in folgender Verteilung: 35.3 ± 3.6% im Nebenhodenkopf, 16.9 ± 1.7% im Nebenhodenkörper und 47.7 ± 3.7% im Nebenhodenschwanz.     

Stabilization of membrane-associated alpha-L-fucosidase by the human sperm equatorial segment

Previous reports from this laboratory documented the existence of two novel isoforms of α- l -fucosidase in human semen and showed that membrane-associated α- l -fucosidase is cryptically held within the acrosomal compartment and enriched within the sperm equatorial segment. The occurrence of these novel isoforms is provocative. Sperm proteins potentially involved in sperm–egg interactions must maintain their functional integrity as they travel through the female reproductive tract. The goal of this project was to investigate the stability of membrane-associated α- l -fucosidase in human sperm. Whole seminal plasma and Percoll^®purified sperm cell populations were incubated for 72 h at 37 °C, with 5% CO₂ or ambient air. At various times during prolonged incubation, sperm cells were permeabilized with 0.1% Triton^®X-100 and enzyme assays using the fluorogenic substrate 4-MU-fuc were performed to evaluate the stability of both the seminal plasma and membrane-associated α- l -fucosidase. Here, we report seminal plasma α- l -fucosidase activity rapidly decreased within 24 h. Conversely, α- l -fucosidase activity from Percoll^® purified sperm cell populations persisted up to 72 h. Data from these experiments support the notions that (i) membrane-associated α- l -fucosidase is stable for extended periods of time, consistent with a possible role in sperm–egg interaction and (ii) membrane domains and compartmentalization within the human sperm are key to preserving protein integrity.     

Influence of urogenital infections on sperm functions

Summary. Many studies have examined the impact of genital tract infections on male fertility; however, the effect of bacteriospermia on sperm quality is still controversial. Bacterial infections are more frequently found in semen samples from asymptomatic infertile patients than in those from fertile men. Bacteriospermia is also a common problem of male partners from couples undergoing IVF. Therefore, the effects of microorganisms on human sperm acrosome reaction of oocytes have been studied in vitro and in vivo.
Incubation of spermatozoa with Escherichia coli or Mycoplasma hominis in vitro resulted in reduced sperm motility and inducibility of acrosome reaction (ΔAR) after exposure to calcium ionophore A23187. To show possible effects of E. coli and mycoplasma species on sperm functions in vivo , data from 488 patients were evaluated, in whose ejaculates microbiological examinations and determinations of acrosome reaction after exposure to low temperature had been performed. U. urealyticum and E. coli were found in semen samples from 52 and 31 men, respectively. M. hominis was only present in a minor number of samples and was not included in this study. Semen concentrations of E. coli and U. urealyticum ranged between 500–100000 cfu x ml⁻¹ and 100–80000 cfu x ml⁻¹. No correlation was found between ΔAR and concentration of bacteria (Spearman rank correlation coefficient, E. coli : r-0.081, P = 0.6644; U. urealyticum : r = -0.081, P = 0.5698).
In 69% of cases with U. urealyticum infection and reduced inducibility of acrosome reaction, this sperm function was normal after antibiotic therapy. However, improvement of acrosomal function may only be due to intra-individual variations of acrosome reaction. While E. coli and mycoplasma species affect sperm functions in vitro , the present data and a review of the literature fail to demonstrate similar effects in vivo.     

Absorption pharmacokinetics of clonidine nasal drops in children

Background:  The α2 agonist clonidine has become a popular drug for premedication in children. Effects and pharmacokinetics after oral, rectal, and intravenous administration are well known. The aim of this study was to investigate the absorption pharmacokinetics of clonidine nasal drops in children.
Methods:  Thirteen ASA I pediatric patients received after induction of anesthesia 4 mcg·kg⁻¹ of clonidine by the nasal route. Blood samples were taken during a 12-h period and plasma levels of clonidine were analyzed by liquid chromatography–mass spectrometry. Data were calculated by a computer-aided curve-fitting program.
Results:  Plasma pharmacokinetics following administration of clonidine nasal drops showed a considerable interindividual variability and absorption was delayed and limited. A total of 95% confidence intervals for maximum plasma concentration and time to achieve maximum plasma concentration were 0.4–0.6 ng·ml⁻¹ and 1.4–3.0 h, respectively.
Conclusions:  Clonidine nasal drops are erratically absorbed from the nasal mucosa and, thus, this mode of drug administration is not recommended for premedication purposes.     

The effect of lidocaine on remifentanil-induced cough

This study was performed to investigate the incidence of remifentanil-induced cough and evaluate the efficacy of lidocaine on its prevention. Five-hundred patients, aged 18–70 years, were randomly allocated into two groups to receive either lidocaine 0.5 mg.kg⁻¹ or 0.9% normal saline intravenously 1 min before remifentanil administration at a target effect-site concentration of 4 ng.ml⁻¹. Any episode of cough was classified as coughing and graded as mild (1–2), moderate (3–4) or severe (5 or more). We found that the overall incidence of cough was significantly higher in the saline group (69 patients; 27.6%) than that in the lidocaine group (38 patients; 15.2%) (p   <   0.001). The results of logistic regression indicated that age and smoking were associated with remifentanil-induced cough. This study demonstrated that intravenously administered lidocaine 0.5 mg.kg⁻¹ effectively suppresses remifentanil-induced cough without possible systemic lidocaine toxicity.     

Pharmacokinetic–pharmacodynamic modeling of the hypotensive effect of remifentanil in infants undergoing cranioplasty

Objectives:  Although remifentanil has been used to induce hypotension during surgery in infants, no pharmacokinetic–pharmacodynamic (PKPD) model exists for its quantitative analysis. Our aim was to determine the quantitative relationship between whole blood remifentanil concentration and its hypotensive effect during surgery in infants.
Methods/materials:  We studied seven infants (age 0.3–1 year) who underwent cranioplasty surgery and received remifentanil delivered by a computer-controlled infusion pump during the maintenance of anesthesia. Arterial blood samples to determine remifentanil concentration and mean arterial blood pressure (MAP) measurements were collected. A simultaneous PKPD mixed-effects model was built in NONMEM.
Results:  A total of 77 remifentanil concentrations and 185 MAP measurements were collected. Remifentanil pharmacokinetics was described with a two-compartment model, parameter estimates were 2.99 l·min⁻¹·70 kg⁻¹ for clearance and 16.23 l·70 kg⁻¹ for steady state volume of distribution. Mean baseline MAP was 69.7 mmHg and was decreased as per clinical requirements. A sigmoidal E _max model driven by an effect compartment described the decrease in MAP, with an estimated concentration to decrease MAP by half (EC₅₀) being 17.1 ng·ml⁻¹.
Conclusions:  Remifentanil is effective in causing hypotension. The final model predicts that a steady state remifentanil concentration of 14 ng·ml⁻¹ would typically achieve a 30% decrease in MAP.