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Biomedical subjects

J J Driessen

Publications and source records attributed to J J Driessen.

At least 19 recordsLinked to original sources

Time course of action of sugammadex (Org 25969) on rocuronium-induced block in the Rhesus monkey, using a simple model of equilibration of complex formation.

BACKGROUND: Reversal of neuromuscular block can be accomplished by chemical encapsulation of rocuronium by sugammadex (Org 25969), a synthetic gamma-cyclodextrin derivative. The present study determined the time course of the reversal action of sugammadex on rocuronium-induced block in the anaesthetized Rhesus monkey using train-of-four stimulation. METHODS: A bolus injection of rocuronium 100 microg kg(-1) (about 1xED(90)) was given to determine the degree of neuromuscular block reached by this dose. After complete spontaneous recovery, a rapid bolus injection of sugammadex, 1 mg kg(-1), was given and at different time intervals (15, 30 or 60 min, in three different experiments) the effect of another rocuronium bolus injection of 100 microg kg(-1) was determined. RESULTS: Injection of the first dose of rocuronium resulted in a mean neuromuscular block (depression of first twitch) of 93 (SEM=1.6)%. Fifteen minutes after injection of sugammadex the same rocuronium dose resulted in 17% (SEM=5.6) block. After 30 and 60 min these maximum blocks amounted to 49% (SEM=7.6) and 79% (SEM=4.2), respectively. The estimated half-life of sugammadex in Rhesus monkey is 30 (SEM=4.9) min. CONCLUSIONS: The half-life of sugammadex (Org 25969), a new fast and efficient reversal agent for rocuronium-induced block, is relatively short in the Rhesus monkey, implying the possibility to perform neuromuscular block by rocuronium shortly after reversal of a prior block. In translation to the human situation differences in rocuronium sensitivity and kinetics should be taken into account.

Androstanols↗

Depth of the thoracic epidural space in children.

Thoracic epidural anaesthesia in anaesthetized children requires a meticulous technique and may have an increased success rate when the distance between skin and epidural space is known. The objective of this observational study was to measure the skin to epidural distance (SED) during thoracic epidural puncture in 61 children. The epidural puncture was performed using the loss of resistance technique with saline 0.9%. The distance from the needle tip to the point where the needle emerged from the skin was measured. The post-operative analgesia parameters were also measured. Skin to epidural distance correlated significantly with the age and weight of the children. The equation for the relation between SED (cm) and age was 2.15 + (0.01 x months) and for SED vs weight was 1.95 + (0.045 x kg). Despite considerable variability among individuals, the observed correlation of SED with both age and weight shows that this parameter may be helpful to guide thoracic epidural puncture in anaesthetized children.

Adolescent↗

Pharmacokinetics and pharmacodynamics of rocuronium in patients with and without renal failure.

BACKGROUND AND OBJECTIVE: This study clarifies the relationship between the neuromuscular blocking effects of rocuronium 0.6 mg kg(-1) and its pharmacokinetics in patients with renal failure. METHODS: Seventeen healthy patients and 17 patients with renal failure were studied under propofol anaesthesia in this prospective open label study. Rocuronium 0.6 mg kg(-1) was given after induction of anaesthesia. The train-of-four mechano-myographic response of the thumb to supramaximal stimulation of the ulnar nerve at 2 Hz every 12 s was measured. Venous blood samples (4 mL) were obtained at 0, 2, 4, 7, 10, 15, 20, 30, 60, 120, 180, 240 and 360 min after relaxant administration. Samples were centrifuged, separated and stored at -20 degrees C until plasma levels of rocuronium and its metabolites were measured. Two- and three-exponential equations were used to describe the pharmacokinetic data in each group and these were compared to each other using the Wilcoxon signed rank sum test as was the pharmacodynamic data. P < 0.05 was significant. RESULTS: Onset of block was similar in both groups. Clinical duration and the time to recovery of the train-of-four to 70% were prolonged in the renal failure group compared to control; 49 vs. 32 min (P < 0.004, 95% confidential, interval 17, difference 5-28) and 88 vs. 55 min (P < 0.001, 95% confidential interval 33, difference 17-50), respectively. Clearance of rocuronium was reduced by 39% in the renal failure patients compared to control, with an 84% increase in the mean residence time. The volume of distribution was unaffected by renal failure. CONCLUSIONS: The duration of action of a bolus dose of 0.6 mg kg(-1) rocuronium is increased significantly in patients with end-stage renal failure compared to healthy controls. This increase may be due to a decreased clearance of rocuronium, the disease process causing the renal failure and/or the medication which patients with renal failure need in their treatment.

Adolescent↗

Acceleromyography in neonates and small infants: baseline calibration and recovery of the responses after neuromuscular blockade with rocuronium.

BACKGROUND: We have evaluated the use of the TOF-Guard (TOF, train-of-four) acceleromyographic thumb responses to ulnar nerve stimulation in neonates and infants and the return of the responses after neuromuscular blockade. METHODS: Baseline acceleromyographic recording of thumb adduction to ulnar nerve stimulation during volatile anaesthesia was performed in 22 babies aged less than 30 weeks. At the start of stimulation the automatic set-up procedure of the TOF-Guard was used to see if a 100% control twitch height could be achieved. Irrespective of the ability to achieve a 100% control twitch height, TOF stimulation was used thereafter. When no automatic 100% control twitch could be reached, the transducer signal gain factor was set manually to obtain a 100% value. In 14 of the 22 children the recovery after neuromuscular blockade with rocuronium 0.3 mg kg(-1) was recorded. RESULTS: In nine of 22 patients a 100% baseline twitch height was obtained with the automatic set-up. In the other 13 babies the TOF-Guard display indicated that the transducer signal was too low. The mean time to recovery of control twitch to 75% of baseline after rocuronium 0.3 mg kg(-1) was 51 min (SD = 21) and the time to recovery of the TOF ratio to 70% was 49 min (SD = 19). The mean final twitch height and TOF after recovery from rocuronium blockade were 101% (SD = 15) and 92% (SD = 12), respectively. CONCLUSION: The recovery of the responses after neuromuscular blockade to near baseline values shows that acceleromyography can be used to measure neuromuscular block and recovery in neonates and infants.

Androstanols↗

Pharmacodynamics of rocuronium 0.3 mg kg(-1) in adult patients with and without renal failure.

BACKGROUND AND AIM: The neuromuscular effects of a bolus dose of rocuronium 0.6 mg kg(-1) under propofol anaesthesia in renal failure patients are prolonged compared to healthy patients. The present study aims to describe the neuromuscular effects of 0.3 mg kg(-1) rocuronium under propofol anaesthesia in patients with renal failure and to compare these effects with healthy control patients. METHODS: With institutional approval and informed consent, 18 healthy patients and 18 patients with renal failure took part in this prospective open label study. The renal failure patients were undergoing either renal transplantation or insertion of a shunt. Rocuronium 0.3 mg kg(-1) was given intravenously after induction of anaesthesia with propofol 1-2 mg kg(-1) and fentanyl 2 microg kg(-1). Propofol 6-12 mg kg(-1) h(-1) was used for maintenance of anaesthesia. Four acceleromyographic responses of the thumb after supramaximal stimulation of the ulnar nerve using surface electrodes at 2 Hz every 15 s were measured and recorded. The onset time, the time to recovery of the first twitch to 25% recovery and the time to a train-of-four ratio of 0.7 were all recorded. Wilcoxon rank sum testing was used to compare the pharmacodynamics and to see if medication, gender or electrolytes influenced the duration of the block. P < 0.05 was significant. RESULTS: No statistical differences were seen in the neuromuscular blocking effects of rocuronium between the two groups but there was a significant difference (P < 0.00001) in the variability of the total duration of the block. CONCLUSIONS: Rocuronium 0.3 mg kg(-1) is suitable for use in patients with renal failure when endotracheal intubation and neuromuscular block for a short period of time are needed. Tracheal intubation is facilitated within 4 min and the block can be antagonized within 20 min.

Adult↗

Anesthetic management in a child with Arnold-Chiari malformation and bilateral vocal cord paralysis.

We report a case of a child who was scheduled for an emergency ventriculoperitoneal shunt procedure. The patient had a type II Arnold-Chiari malformation (ACM) and associated hydrocephalus and presented with near complete respiratory obstruction from bilateral abductor vocal cord palsy. Early diagnosis and management of airway abnormalities associated with ACM may be lifesaving. Chiari malformations and anesthesia management are discussed.

Airway Obstruction↗

Suxamethonium administration prolongs the duration of action of subsequent rocuronium.

BACKGROUND AND AIM: Rocuronium may be given to patients for intubation and also after they have received suxamethonium for intubation. The neuromuscular profile of rocuronium given after recovery from suxamethonium may not be identical to that when rocuronium has been given alone. The neuromuscular effects of suxamethonium and rocuronium, and their effects on intraocular pressure (IOP), heart rate (HR) and arterial pressure were also recorded. METHODS: Thirty patients were randomly allocated to receive either 0.6mg kg(-1) rocuronium (n = 15) or 1 mg kg(-1) suxamethonium (n = 15) for intubation. Anaesthesia was first induced using propofol 2.5 mg kg(-1) and fentanyl 2 microg kg(-1) and maintained with propofol 6-12 mg kg(-1) h(-1). The response of the thumb to supramaximal train-of-four (TOF) ulnar nerve stimulation at the wrist was measured using a mechanomyograph. In the suxamethonium group, when the first twitch of the TOF had recovered to 90%, rocuronium 0.6 mg kg(-1) was administered. Before administration of relaxant, baseline readings of HR, arterial pressure and IOP were measured until stable, then the appropriate relaxant administered. Thereafter, all readings were repeated at 30, 90, 150, 210 and 270 s. Tracheal intubation was performed 300 s after the intubating dose and all recordings repeated 30 s later. Mechanomyographic monitoring was continued until 70% TOF recovery. RESULTS: Suxamethonium had a more rapid onset than rocuronium (49s vs. 74s, P < 0.0001). The onset time of rocuronium after suxamethonium was significantly reduced (56 s) and the time to recover to a TOF of 70% following rocuronium was increased by previous suxamethonium administration (47 vs. 58 min, P < 0.05). Suxamethonium caused a marked rise in IOP (>30%) and HR (>10%) while rocuronium had little effect on either. CONCLUSION: Previous suxamethonium administration decreases the onset time and increases the duration of action of rocuronium. Unlike suxamethonium, rocuronium has few cardiovascular effects and causes little change in IOP.

Adult↗

Severe myocardial ischaemia during mask induction of anaesthesia in an infant with unknown critical supravalvular aortic stenosis.

Congenital supravalvular aortic stenosis is an uncommon type of aortic obstruction. When critical, it represents an extreme variant of outflow tract obstruction with increased risk of cardiovascular instability during exercise or anaesthesia. We present a case of severe myocardial ischaemia during induction of anaesthesia with sevoflurane in a 3-month baby with a presumed diagnosis of valvular aortic stenosis for which a percutaneous balloon dilatation of the aortic valve was scheduled.

Anesthesia, Inhalation↗

Clinical letter: epidural analgesia in a newborn with Hirschsprung's disease, associated with congenital central hypoventilation syndrome.

A case is presented of a neonate with Hirschsprung's disease, associated with congenital central hypoventilation syndrome. After an ileostomy (at 2 days) and a stoma revision (at 10 days), postoperative pain management was established by continuous intravenous infusion of morphine, which caused severe postoperative respiratory depression. At 6 weeks a re-exploration and stoma revision was performed using postoperative epidural analgesia with bupivacaine. This caused no respiratory depression. A colectomy under epidural analgesia at 8 months was also uneventful. Respiratory difficulties in children with congenital central hypoventilation syndrome associated with Hirschsprung's disease are discussed in relation to the technique of choice for postoperative pain management.

Analgesia, Epidural↗

The time-course of action and recovery of rocuronium 0.3 mg x kg(-1) in infants and children during halothane anaesthesia measured with acceleromyography.

This study compares the time-course of action of neuromuscular paralysis after 0.3 mg x kg(-1) of rocuronium during nitrous oxide-halothane anaesthesia in children of three different age groups. With appropriate approval and informed consent from the parents, 51 children, ASA I-II, scheduled for elective surgery requiring muscle relaxation, were studied. The children were assigned to three groups according to age: group 1, 0-6 months; group 2, 6-24 months; and group 3, > 24 months of age. Induction of anaesthesia and tracheal intubation were performed under halothane anaesthesia. Acceleromyography of the thumb was recorded after supramaximal transcutaneous ulnar nerve stimulation using train-of-four (TOF) stimulation. Rocuronium 0.3 mg x kg(-1) was given as a rapid i.v. bolus prior to surgical incision. The onset time (time to max effect) and the maximal depth of the block, the time to recovery of the first twitch (T1) to 25% and 75% of its baseline, the recovery index (RI), and the time to recovery of the TOF ratio to 70% after the end of injection of rocuronium were all measured. The mean (SD) age of the children in groups 1, 2, and 3 was 3.1 (1.6), 12.6 (3.7), and 63 (46) months, respectively. The onset time of rocuronium was 47 (12), 83 (42) and 94 (12) s, respectively, in groups 1, 2, and 3 (P<0.05 group 1 vs. 2 and 3). One hundred percent block was achieved in 18/19 patients in group 1, 12/14 in group 2 and 6/18 in group 3. The times to 25% and 75% recovery of T1 and the time for recovery of the TOF ratio to 70% were all significantly longer in groups 1 and 2 compared to group 3. Group 1 and 2 showed no significant differences in recovery times. The RI was significantly prolonged in group 1 versus 3. The authors conclude that rocuronium 0.3 mg x kg(-1) during halothane anaesthesia causes more neuromuscular depression and has a longer duration of action in infants than in children older than 2 years.

Aging↗

Evaluation of the electroencephalographic bispectral index during fentanyl-midazolam anaesthesia for cardiac surgery. Does it predict haemodynamic responses during endotracheal intubation and sternotomy?

The bispectral index, a value derived from the electroencephalogram, has been proposed as a measure of anaesthetic effect. The aim of the present study was to evaluate the bispectral index during midazolam-fentanyl anaesthesia for cardiac surgery for its possible role as a predictor of increases in systolic blood pressure during endotracheal intubation and sternotomy. After institutional approval 15 consenting patients, scheduled for elective cardiac surgery, were selected for the study. Anaesthesia was induced in all patients with a loading dose of fentanyl 7.5-10 micrograms kg-1, midazolam 0.15 mg kg-1 and pancuronium 0.1 mg kg-1. After a further bolus dose of fentanyl 10-12.5 micrograms kg-1 prior to the start of incision and sternotomy, maintenance infusion rates of fentanyl 4-6 micrograms kg-1 h-1 and midazolam 0.1 mg kg-1 h-1 were started and continued through surgery at the discretion of the anaesthetist and guided by the presenting clinical and haemodynamic responses. The control of anaesthesia was never based on the value of the bispectral index. The mean bispectral index value decreased from 95.7 (3.1) at base-line to 59.5 (12.0) after induction of anaesthesia and then remained below 70 throughout surgery. However, there was an important interindividual variability in bispectral index values despite standardized dosages of fentanyl and midazolam. There was no significant correlation between the bispectral index values in the pre-intubation and pre-incision period and the changes in systolic blood pressure during endotracheal intubation and sternotomy, respectively. In conclusion, the large intersubject variability in the bispectral index values should be investigated further in the light of the great variability in the clinical effects of midazolam and fentanyl. The lack of significant correlation between the bispectral index values and the haemodynamic responses suggest that the bispectral index, which is a helpful monitor of anaesthetic depth, is not a very reliable monitor of global anaesthetic adequacy during total intravenous anaesthesia with a combination of midazolam and fentanyl in cardiac surgical patients.

Adjuvants, Anesthesia↗

Accelerated recovery and disposition from rocuronium in an end-stage renal failure patient on chronic anticonvulsant therapy with sodium valproate and primidone.

An end-stage renal failure patient, receiving chronic treatment with the anticonvulsants, sodium valproate and primidone, showed accelerated recovery with enhanced elimination (T1/2(z) = 52 min) and clearance (Cl = 14.4 ml min-1 kg-1) of rocuronium. The pharmacokinetic and pharmacodynamic effects of rocuronium in this patient are compared with those published for healthy and renal failure patients. Increased hepatic binding of rocuronium rather than metabolism is suggested as the possible cause of this effect.

Adult↗

Comparison of isoflurane and midazolam as hypnotic supplementation to moderately high-dose fentanyl during coronary artery bypass grafting: effects on systemic hemodynamics and early postoperative recovery profile.

OBJECTIVE: The aim of this study was to compare isoflurane and midazolam as hypnotic adjuncts to moderately high-dose fentanyl during coronary artery bypass grafting (CABG) with regard to perioperative hemodynamics and early postoperative recovery profile. DESIGN: Prospective open randomized clinical trial. SETTING: Single university-affiliated medical center. PARTICIPANTS: Thirty patients scheduled for elective primary CABG were randomly divided into two groups receiving either isoflurane or midazolam as adjuncts to 50 micrograms/kg of fentanyl. INTERVENTION: Anesthesia was induced with intravenous fentanyl, 10 micrograms/kg, and midazolam, 0.1 mg/kg, and maintained with either isoflurane, 0.6% or midazolam, 0.1 mg/kg/hour, in intravenous infusion. Before the sternotomy, all patients received 30 micrograms/kg of fentanyl. Midazolam and isoflurane were stopped at the start of cardiopulmonary bypass (CPB). At rewarming, all patients received fentanyl, 5 to 10 micrograms/kg, and either isoflurane, 0.6%, or midazolam, at a reduced rate of 0.05 mg/kg/h. Changes in systolic blood pressure of more than 20% from baseline were first treated with vasoactive drugs. Hypertension was corrected with ketanserin, 10 to 20 mg; hypotension with ephedrine, 5 mg. For a mean blood pressure of less than 50 mmHg during CPB phenylephrine, 0.25 to 0.5 mg, was administered. When hypotension persisted despite a vasopressor, the administration of midazolam or isoflurane was stopped. Postoperatively, the patients were mechanically ventilated overnight and sedated with intermittent doses of fentanyl, 0.15 mg, and midazolam, 5 mg. MEASUREMENTS AND MAIN RESULTS: Routine five-lead electrocardiogram (ECG) and invasive hemodynamic monitoring using a pulmonary artery catheter were performed. The mean dose of fentanyl was 3.9 mg in the midazolam group versus 3.6 mg in the isoflurane group. There were no significant perioperative differences between groups in cardiac output, filling, or pulmonary artery pressures. Systolic blood pressure from the initial incision to CPB was lower in the isoflurane group compared with the midazolam group. During this interval, ketanserin was required in nine patients from the midazolam group at a mean dose of 26 mg, compared with only one patient in the isoflurane group. During and after CPB, there was no difference in ketanserin and in vasopressive/inotropic agent requirements. Temporary cessation of midazolam was required in four patients, for a mean of 34 minutes; whereas isoflurane was stopped in 10 patients for 36 minutes, mostly in the post-CPB period. Time to awakening and to extubation in the midazolam group (217 minutes and 19.5 hours) and the isoflurane group (193 minutes and 18.2 hours) were comparable. Between intensive care unit (ICU) admission and extubation, the patients in the midazolam group received 0.89 mg of fentanyl and 36.5 mg of midazolam compared with 0.98 mg of fentanyl and 36.2 mg of midazolam in the isoflurane group. There was a tendency for a higher postoperative pulmonary shunt and more severely impaired oxygenation in the isoflurane group. CONCLUSION: Midazolam supplementation to fentanyl required more frequent antihypertensive escape during the pre-CPB period than isoflurane. However, more frequent cessation of isoflurane caused by hypotension was needed in the post-CPB period. No difference in awakening and ICU discharge was found.

Aged↗

Pulsatile compared with nonpulsatile perfusion using a centrifugal pump for cardiopulmonary bypass during coronary artery bypass grafting. Effects on systemic haemodynamics, oxygenation, and inflammatory response parameters.

The present study investigated the influence of pulsatile or nonpulsatile flow delivery with a centrifugal pump for cardiopulmonary bypass (CPB) during coronary artery bypass grafting (CABG) in two randomized groups of 19 patients each. All patients received a standard anaesthetic and surgical protocol. Pulsatile perfusion during CPB was created by accelerating the baseline pump speed of the Sarns centrifugal pump at a rate of 50 cycles per minute. Measurements included perioperative systemic haemodynamics and oxygen exchange, total haemolytic complement (CH50), polymorphonuclear (neutrophil) granulocyte (PMN) count and plasma granulocyte elastase bound to alpha 1-proteinase inhibitor (E-alpha 1-PI). Laboratory measurements were corrected for haemodilution. During and after CPB there were only a few significant differences between the groups in systemic haemodynamics and oxygenation, i.e. a lower mean arterial blood pressure after the end of CPB in the nonpulsatile group (65 mmHg, SD = 11 vs 76 mmHg, SD = 11) and a lower SvO2 during rewarming on CPB in the nonpulsatile group (62%, SD = 8 vs 67%, SD = 8). The decrease in percentage of PMNs in the total white blood cell count during CPB was greater in the nonpulsatile group than in the pulsatile group (from 61 to 46% vs 63 to 53% of prebypass value). The steep increase of PMN count at the end of CPB and postoperatively was comparable in both groups. The maximal decrease of CH50 levels, occurring after surgery, was significantly higher in the nonpulsatile group (70% SD = 15 vs 79%, SD = 16, of baseline value), suggesting a greater complement activation. E-alpha 1-PI levels increased significantly in both groups during and after CPB with higher peak levels, obtained at one hour after admission to an intensive care unit, in the nonpulsatile group (316 micrograms/l, SD = 102) than in the pulsatile group (247 micrograms/l, SD = 106). There was a partly inverse correlation between the peak postoperative elastase levels and the PaO2/FiO2 ratios at the first postoperative morning. This ratio was significantly lower in the nonpulsatile group (211, SD = 56) than in the pulsatile group (247, SD = 62). Postoperative respiratory tract infection was more frequent in the nonpulsatile group (n = 9) than in the pulsatile group (n = 2). Adding a pulsatile component to centrifugal blood pumping during CPB may have benefits with regard to the possibly detrimental whole body inflammatory response to CPB. Further studies are warranted to investigate whether these differences will affect clinical outcome.

Aged↗

Comparison of the standard roller pump and a pulsatile centrifugal pump for extracorporeal circulation during routine coronary artery bypass grafting.

The present prospective study compared the standard nonpulsatile twin roller pump with the Sarns centrifugal pump, in the pulsatile mode, as arterial pumps for extracorporeal circulation during coronary artery bypass grafting (CABG). The study was conducted in two consecutive groups of 25 patients receiving a standard anaesthetic and surgical protocol. The investigated parameters included haemodynamic profiles, oxygen exchange, blood gas and acid-base homeostasis, haematology, coagulation and complement consumption. With comparable settings for pump flow, gas flow and delivered oxygen concentrations, there was no difference between the groups in the main haemodynamic parameters during cardiopulmonary bypass (CPB). However, a tenfold lower dose of sodium nitroprusside was required to keep systemic vascular resistance within physiologic limits during CPB in the centrifugal group (C group) compared with the roller group (R group). During rewarming oxygen extraction was higher in the C group than in the R group. During the first eight hours after CPB no differences in haemodynamics, oxygenation parameters and pulmonary shunt between the groups were observed. During, as well as after, CPB there was no significant difference in blood gas and acid-base homeostasis between either group. Average postoperative blood loss via chest tubes, total transfusions of blood products, haemoglobin and coagulation did not differ between the two groups. However, the white blood cell count, corrected for changes in haematocrit, decreased during the early phase of CPB in the R group, but not in the C group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The effects of acute changes in renal function on the pharmacokinetics of midazolam during long-term infusion in ICU patients.

This study investigated the pharmacokinetics of midazolam and its main metabolite, 1-hydroxymethylmidazolam glucoronide, during long-term i.v. infusion in 39 mechanically ventilated ICU patients of whom 6 were in acute renal failure (ARF). The mean infusion rate of midazolam was similar (9.4 vs 8.7 mg/h) in the control patients and those with ARF. The renal clearance of 1-hydroxymethylmidazolam glucuronide was much lower in the ARF group than in the control group (3.9 vs 136 ml/min). Consequently, its plasma elimination half-life after discontinuation was also greatly prolonged, but this shouldn't cause very prolonged sedative effects since this metabolite is much less active than the parent drug. However, the half-life of midazolam itself was also significantly longer in patients with ARF than in the control group (13.2 vs 7.6 h). Apparently, this was caused by a combination of a slightly lower total clearance and a higher volume of distribution. Therefore, regular reassessment of the degree of sedation and appropriate adaptation of the infusion rate of midazolam are recommended in ICU patients with ARF.

Acute Kidney Injury↗