Compartmental pharmacokinetics of nefopam during mild hypothermia.

BACKGROUND: Nefopam is a non-opioid, non-steroidal, centrally acting analgesic which has an opioid-sparing effect. It also reduces the threshold (triggering core temperature) for shivering without causing sedation or respiratory depression. The drug is therefore useful as both an analgesic and to facilitate induction of therapeutic hypothermia. However, compartmental pharmacokinetics during hypothermia are lacking for nefopam. METHODS: We conducted a prospective, randomized, blinded study in eight volunteers. On two different occasions, one of two nefopam concentrations was administered and more than 30 arterial blood samples were gathered during 12 h. Plasma concentrations were determined using gas chromatography/mass spectrometry to investigate the pharmacokinetics of nefopam with non-linear mixed-effect modelling. RESULTS: A two-compartment mammillary model with moderate inter-individual variability and inter-occasional variability independent of covariates was found to best describe the data [mean (SE): V(1)=24.13 (2.8) litre; V(2)=183.34 (13.5) litre; Cl(el)=0.54 (0.07) litre min(-1); Cl(dist)=2.84 (0.42) litre min(-1)]. CONCLUSIONS: The compartmental data set describing a two-compartment model was determined and could be implemented to drive automated pumps. Thus, work load could be distributed to a pump establishing and maintaining any desired plasma concentration deemed necessary for a treatment with therapeutical hypothermia.

Withdrawal forces of lumbar spinal catheters: no dependence on body position.

BACKGROUND: Spinal catheters, because of their smaller diameter, have lower tensile strength than epidural catheters. This study was designed to measure the withdrawal forces needed to remove lumbar spinal catheters and to determine whether patient position affects withdrawal forces. METHODS: Eighty-two patients with a 24-gauge spinal catheter placed midline at the lumbar L3/4 or L4/5 level were randomly assigned to catheter removal either in flexed lateral or sitting position. Withdrawal forces were measured using a tension spring balance. RESULTS: Mean withdrawal force was 0.91 N (95% CI: 0.73, 1.09) with extremes up to 5 N. Withdrawal force in the flexed lateral position was 1.04 N (95% CI: 0.73, 1.34) or in the sitting position was 0.78 N (95% CI: 0.59, 0.97). The 95% CI for the difference of the means was -0.62 N, 0.10 N. Thus, the absolute mean difference between the positions can be assumed to be smaller than 0.62 N. Neither the length of the spinal catheter under the skin or in the subarachnoid space, nor BMI influenced withdrawal force. CONCLUSION: Withdrawal force of spinal catheters is not influenced by body position during catheter removal, length of catheter under skin, or BMI.

Perioperative concentrations of catecholamines in the cerebrospinal fluid and plasma during spinal anesthesia.

BACKGROUND: Catecholamine release is a physiological response to stress. The extent to which perioperative stress provokes the central release of catecholamines, which modulate pain perception in the spinal cord, still remains unknown. The perioperative course of catecholamine concentrations in the cerebrospinal fluid (CSF) and plasma was examined. METHODS: A prospective study was performed in 25 patients (ASA III, 60-84 years) undergoing elective hip joint replacement in spinal catheter anesthesia. The concentrations of dopamine, epinephrine and norepinephrine in the CSF and plasma were measured before anesthesia, immediately after surgery, and 6 and 24 h post-operatively. RESULTS: In most patients, dopamine and epinephrine were not detectable in CSF. CSF-norepinephrine concentrations decreased from median [interquartile-range] 159 [124;216] pre-anesthesia to 116 [79;152] pmol/l immediately post-operatively and were slightly elevated 24 h post-operatively (180 [134;302] pmol/l) (P=0.05). Dopamine plasma concentrations were not detectable or were barely above the detection threshold. Plasma epinephrine increased from 61 [28;77] pmol/l pre-anesthesia to 112 [69;138] pmol/l 6 h post-operatively and returned to baseline 24 h post-operatively (P=0.001). Plasma norepinephrine concentrations increased intra-operatively from 298 [249;422] to 556 [423;649] pmol/l and remained elevated 24 h after surgery (P=0.009). There was no association between changes in CSF or plasma norepinephrine or epinephrine concentrations and changes in heart rate (HR) or mean arterial pressure (MAP). CONCLUSION: During spinal anesthesia for elective hip joint replacement, norepinephrine concentrations were greater in plasma than in CSF. CSF dopamine and epinephrine concentrations were essentially undetectable. The changes in CSF-norepinephrine concentrations and the changes of plasma norepinephrine concentrations showed no association with each other; nor were there correlations between clinical stress parameters (HR, MAP) or visual analog scale pain, and the changes in CSF norepinephrine concentrations.

The blood supply of the scaphoid bone.

Scaphoid vascularisation was investigated using macroscopic and microscopic techniques in 12 uninjured, formalin fixed cadaver hands. A good blood supply of the scaphoid bone from palmar, dorsal and radial vessel groups with a variety of anastomoses was found which should provide sufficient collateral blood flow from adjacent regions in some patients. Since blood supply is available from the palmar circulation, a dorsal approach to the scaphoid bone is possible.

Target-controlled infusion of propofol for fibreoptic intubation.

BACKGROUND AND OBJECTIVE: In a retrospective study, we examined the suitability of a departmental clinical protocol for anaesthesia induction with target-controlled infusion of propofol developed for fibreoptic intubation in spontaneously breathing patients scheduled for outpatient oral surgery at the dental clinic of the Vienna University Hospital. METHODS: Propofol was administered using target-controlled infusion (Diprifusor) at increasing target plasma concentrations starting at 2.5 microg mL(-1). After 10 min, an intravenous dose of alfentanil (5-10 microg kg(-1)) was given for pain reduction. After a further 2 min, the patient was evaluated for response to auditory stimulation. If unresponsive, fibreoptic intubation was performed, otherwise the target concentration was increased by 0.2 microg mL(-1) every 2 min until non-responsiveness was attained. RESULTS: Tracheal intubation was successful in all patients without any haemodynamic instability. However, one patient required facemask ventilation for 2 min. No patient was aware of intubation. The plasma concentration required for non-responsiveness was 2.8 +/- 0.4 microg mL(-1) (mean +/- SD). CONCLUSIONS: When using a target-controlled infusion of propofol, fibreoptic intubation can be performed with complete amnesia of the procedure for the patient. However, assisted ventilation of the lungs may be necessary as spontaneous ventilation may cease.

[A possible risk for geriatric risk patients caused by intraoperative disorder of cerebral energy utilization?]. / Ein mögliches Risiko für geriatrische Risikopatienten durch eine intraoperative Störung der zerebralen Energieutilisation?

OBJECTIVE: This study was carried out on cerebrospinal fluid (CSF) to investigate the perioperative course of certain ischaemic markers, namely neurone-specific enolase (NSE), creatine kinase (CK-BB), hypoxanthine, and lactate in order to identify a disturbed cerebral energy utilisation which could be responsible for the development of temporary mental dysfunctions. Those dysfunctions are characterised by preserved memory content and perception, but the coordination and association of these functions are disturbed. Typical clinical signs are motor restlessness, disordered emotions, and symptoms of dementia. Little is known about the aetiology of those symptoms, but they are most likely due to various events, such as direct drug effects, the extent of surgical trauma, sensorial deprivation, and disturbed perfusion. METHODS: Eight orthopaedic patients (ASA III or IV) scheduled for removal of their total hip replacement were anaesthetised by catheter-spinal anaesthesia (CSA) for pain relief in combination with standardised, modified neuroleptanalgesia (NLA). At six defined times (15 hours preoperatively, immediately before and after surgery and 6, 24, and 36 hours postoperatively) CSF samples were drawn and the ischaemic markers were determined by means of radioimmunoassay (NSE), electrophoresis (CK-BB), photometry (lactate), and high-pressure liquid chromatography (hypoxanthine). The release of ischaemic markers into CSF correlates linear with the extent of ischaemic brain damage. RESULTS: Mean concentrations of the following ischaemic markers increased in all patients intraoperatively: NSE from 12.3 ng/ml to 13.4 ng/ml, hypoxanthine from 1.86 mumol/l to 3.73 mumol/l, and lactate from 1.4 mmol/l to 2.0 mmol/l respectively, all of which returned to normal within 36 hours. The CK-BB concentrations were all within normal values and not affected by the operation during this investigation. CONCLUSION: Although no clinical signs of temporary mental dysfunction have been observed, the results indicate that in CSF ischaemic markers temporarily undergo certain changes in their concentrations during the removal of total hip replacements in elderly patients. These changes are reason for assuming that risk patients may suffer a temporary disturbed cerebral energy utilisation intraoperatively, even if stable clinical and cardiovascular conditions prevail under anaesthesia. Such a temporary ischaemic penumbra might be responsible for the postoperative development of temporary mental dysfunctions.

Perioperative changes in cerebral ischemic markers in the cerebrospinal fluid after preoperative nimodipine treatment.

BACKGROUND: Elderly patients with previous organ damage are at risk for minor neurologic deficits after major surgery. Spinal catheter analgesia is used whenever possible in this group and enables regular cerebrospinal fluid (CSF) sampling. Nimodipine, a calcium blocker, may have neuroprotective effects. We examined whether preoperative treatment with nimodipine affects ischemic markers in the CSF during extracranial surgery. METHODS: We performed a prospective, randomized, placebo-controlled, double-blind study in patients (ASA III or IV, 65-85 years) that underwent elective implantation surgery of the hip joint with intrathecal catheter anesthesia. Starting 15 h before surgery, patients received either 30 microg x kg(-1) h(-1) of nimodipine (n = 20) or 0.9% saline solution (placebo, n = 23) as a central venous infusion. The concentrations of neuron-specific enolase, hypoxanthine, creatine-kinase, lactate and pH in the CSF were determined before and immediately after surgery as well as 6 and 24 h after surgery. RESULTS: Before surgery, the baseline CSF pH was normal in all patients. Immediately after surgery it fell significantly to 7.08 +/- 0.29 in the placebo group and non-significantly to 7.27 +/- 0.38 in the treatment group; all values were normalized at 6 and 24 h after surgery in both groups. In the placebo group, lactate levels rose significantly from 1.48 +/- 0.28 mmol l(-1) before surgery to 1.77 +/- 0.27 mmol l(-1) immediately after surgery, and to 2.03 +/- 0.32 mmol l(-1) 24 h after surgery. In the treatment group, lactate concentrations remained stable up to 6 h after surgery (1.55-1.62 mmol l-1), while an increase to 2.10 +/- 0.48 mmol l(-1) was observed 24 h after the operation. Neuron-specific enolase, hypo-xanthine and creatine-kinase showed no change in either group. CONCLUSION: In conclusion, preoperative nimodipine treatment reduced intraoperative CSF acidosis and delayed surgery-related increases in lactate concentration in the CSF by several hours in elderly, comorbid patients at risk for minor postoperative neurologic deficits.

Effects of remifentanil and fentanyl on intraocular pressure during the maintenance and recovery of anaesthesia in patients undergoing non-ophthalmic surgery.

BACKGROUND AND OBJECTIVE: To compare the effects of remifentanil and fentanyl on intraocular pressure during the maintenance and recovery of anaesthesia in patients undergoing elective non-ophthalmic surgery. METHODS: Thirty-two patients (ASA I-II) were randomized into two groups to receive either a continuous infusion of remifentanil (0.25-0.5 microg kg(-1) min(-1), n =16, Group R) or an intermittent bolus of fentanyl (2-5 microg kg(-1), n = 16, Group F) during the maintenance of anaesthesia. For the induction of anaesthesia, Group R received remifentanil 1 microg kg(-1) and Group F received fentanyl 2 microg kg(-1); both groups then received propofol 2 mg kg(-1) with vecuronium 0.1 mg kg(-1). Anaesthesia in both groups was maintained with a continuous infusion of propofol 4-8 mg kg(-1) h(-1). Ventilation of the lungs was controlled to a constant end-tidal PCO2 of 4.7-5.4 kPa. Blood pressure, electrocardiography, heart rate and oxygen saturation were monitored throughout anaesthesia. Intraocular pressure was determined before surgery, during the maintenance of anaesthesia, 2 min after emergence and in the recovery room using a Perkins hand-held applanation tonometer by an ophthalmologist blinded to the anaesthetic technique. RESULTS: After induction of anaesthesia, a significant decrease in intraocular pressure in the remifentanil group from 13.6 +/- 2.6 to 7.1 +/- 3.1 mmHg (P < 0.001) and in the fentanyl group from 13.7 +/- 2.2 to 9.7 +/- 3.4 mmHg (P < 0.001) was observed and maintained during anaesthesia. Thirty minutes after the end of anaesthesia, intraocular pressure returned to baseline values in both groups (remifentanil: 13.9 +/- 2.8 mmHg, P = 0.28; fentanyl: 13.6 +/- 2.3 mmHg, P = 0.59). The intraocular pressure and haemodynamic variables did not differ significantly between the two groups (intraocular pressure, P = 0.7327; blood pressure, P = 0.1295; heart rate, P = 0.8601). CONCLUSIONS: Remifentanil maintains intraocular pressure at an equally reduced level compared with fentanyl.

Effect of different doses of cisatracurium on intraocular pressure in sedated patients.

BACKGROUND AND OBJECTIVE: The aim was to examine the course of intraocular pressure after relaxation with different doses of cisatracurium. METHODS: The investigation was carried out as a prospective, randomized double-blind study in a crossover design in 30 postoperative patients with stable haemodynamic and respiratory function (ASA I and II). To exclude any disrupting factors, patients remained intubated and continuously sedated. Twenty patients received an intubation dose (2 x ED95) of cisatracurium (0.1 mg kg(-1)) compared with atracurium (0.5 mg kg(-1)). In a second series, 10 patients were given an effective dose, ED95 (0.05 mg kg(-1)), and a repeat dose (0.02 mg kg(-1)) of cisatracurium. The intraocular pressure was determined before (T0) as well as 1 (T1), 5 (T5), 10 (T10), 15 (T15), 20 (T20) and 45 (T45) min after bolus administration. RESULTS: Intraocular pressure decreased after an intubation dose of either cisatracurium or atracurium, and reached a minimum after 10 min (6.7 +/- 2.2 and 7.9 +/- 2.1 mmHg, respectively). There was no significant difference between either muscle relaxant (P = 0.27). When lower doses of cisatracurium (0.05 and 0.02 mg kg(-1)) were applied, the intraocular pressure also decreased, albeit to a lesser extent and with a delayed onset (8.4 +/- 1.9 mmHg after 10 min, 9.9 +/- 3.4 mmHg after 15 min). There was no significant difference between dosages (p = 0.44). CONCLUSIONS: Cisatracurium is a useful drug in patients when a decrease of intraocular pressure is wanted and where muscle relaxation is necessary and acceptable.