The effect of prior dural puncture on cerebrospinal fluid sufentanil concentrations in sheep after the administration of epidural sufentanil

Sufentanil is a highly lipid soluble opioid that provides potent analgesia when administered in the subarachnoid space. Unfortunately, the penetration of sufentanil into the cerebrospinal fluid (CSF) after epidural administration is poor, and limits its effectiveness for epidural analgesia. Dural puncture may enhance the movement of epidural sufentanil into the subarachnoid space and increase its effectiveness. To determine whether the administration of epidural sufentanil adjacent to a dural puncture results in significantly greater CSF concentrations, 18 adult ewes were studied. Animals in the control group had an epidural catheter placed at the superior border of the pelvis without dural puncture. Animals in the study group had an epidural catheter placed, followed by a dural puncture performed using an 18-gauge Touhy needle. The dural puncture was performed one interspace cephalad to the epidural catheter. One hour after dural puncture, each animal received a loading dose of 0.35 microg/kg of sufentanil (5 microg/mL) through the epidural catheter, followed by an infusion of epidural sufentanil 0.15 microg x kg(-1) x h(-1) for a period of 4 h. After 4 h, CSF was sampled from a site one interspace caudad to the epidural catheter as well as at the cisterna magna. The mean CSF concentration of sufentanil at the level of the pelvis for animals with a dural puncture was 12.1 +/- 3.0 ng/mL compared with 1.8 ng/mL in controls with intact dura. Sufentanil concentrations at the cisterna magna were below the level of detection (0.08 ng/mL) for all animals in both groups. We conclude that an 18-gauge dural puncture significantly increases movement of sufentanil from the epidural to the intrathecal space. This increase in sufentanil concentration at the level of the pelvis was not associated with detectable levels of sufentanil at the brainstem. Implications: This study addresses the effect of dural puncture on spinal fluid concentrations of sufentanil after epidural administration. A sheep model was used to measure drug concentrations in the spinal fluid at the levels of the pelvis and brainstem after epidural administration. Dural puncture significantly enhanced movement of sufentanil into the spinal fluid at the level of the pelvis, but brainstem concentrations were below the level of detection. Analgesic concentrations of spinal sufentanil in the clinical setting, as well as brainstem concentrations associated with respiratory depression, have yet to be defined.     

Redistribution of sufentanil to cerebrospinal fluid and systemic circulation after epidural administration in dogs

Due to its higher lipid solubility, sufentanil may be less likely than morphine to migrate rostrally in the cerebral spinal fluid (CSF) and cause delayed respiratory depression following epidural administration. However, early respiratory depression has been reported in patients after relatively large doses of epidural sufentanil. This has been attributed to systemic drug uptake. We used a dog model to investigate the pharmacokinetics and rostral spread of epidural sufentanil in CSF. Sampling catheters were placed in the lumbar subarachnoid space, the cisterna magna, and femoral arteries of six mongrel dogs. Samples of cisternal CSF, lumbar CSF, and blood were drawn at 0, 1, 5, 15, 30, 60, 90, 120, and 180 min after lumbar epidural sufentanil injection. We measured sufentanil concentrations by gas chromatography-mass spectrometry and used the least squares method to a fit tri-exponential function to each sufentanil concentration versus time data set. Paired t-test was used to test for statistical significance. After epidural sufentanil, lumbar CSF concentrations were significantly higher than plasma or cisternal CSF sufentanil concentrations at all assessment times. Sufentanil concentrations were significantly higher in cisternal CSF than in plasma at 30 and 60 min after injection. Sufentanil appeared rapidly in lumbar CSF, reaching a maximum concentration (Cmax) of 57 ng/mL at 6.5 min. In cisternal CSF, a Cmax of 1.2 ng/mL was reached at 21 min, and Cmax in plasma was 0.35 ng/mL at 6 min. The area under the concentration-time curve (AUC) of sufentanil in cisternal CSF was approximately six times higher than the plasma AUC (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Apolipoprotein E allelic influence on human cerebrospinal fluid apolipoproteins

A full length cDNA copy of the genomic RNA of lettuce mosaic virus (LMV) was constructed under the control of an enhanced CaMV 35S promoter and of the NOS terminator. This construct was found infectious when inoculated to lettuce plants. The intron II of the bean nitrite reductase gene was engineered into the LMV FL cDNA in order to relieve possible deleterious effects of viral sequences to Escherichia coli cells and to evaluate the effects of the presence of the intron on the FL cDNA infectivity. The intron-less FL cDNA was found to be as stable as its intron-containing counterpart in E. coli. Sequence analysis of progeny RNA derived from plants inoculated with the intron-containing FL cDNA demonstrated that the inserted intron was perfectly spliced out. The symptoms induced in lettuce by either the intron-less or the intro-containing constructs were identical to those caused by the wild-type virus. However a slight delay in the establishment of infection in lettuce and a more obvious lag in Nicotiana benthamiana were observed with the intron-containing FL cDNA.     

Simultaneous recording of cerebrospinal fluid pressure and middle cerebral artery blood flow velocity in patients with suspected symptomatic normal pressure hydrocephalus

Whether anaphylactic histamine release from rat peritoneal mast cells is influenced by betahistine, a histamine H1-receptor agonist/H3-antagonist, and dimaprit, an H2-agonist, was examined. Treatment with dimaprit at 6 and 60 microM for 20 min significantly inhibited the anaphylactic histamine release, whereas betahistine at up to 80 microM under the same conditions did not affect it. Treatment with dimaprit at 6 and 60 microM for 1 to 20 min and for 5 to 20 min, respectively, caused a time-dependent inhibition of the release, but up to 30 min treatment with 8 and 80 microM betahistine had no effect. The decreased histamine release induced by dimaprit was recovered by neither mepyramine nor cimetidine. However, thioperamide, an H3-selective antagonist, dose-dependently restored the diminished release. From these results, the inhibition of anaphylactic histamine release by dimaprit is not produced by the stimulation of H2-receptors, but involves the stimulation of H3-like receptors or H3-subtype receptors, which are distinct from the H3-receptors located in brain, and suggests that the receptor plays an important role in the negative feedback regulation of histamine release.     

Effects of sufentanil on cerebral hemodynamics and intracranial pressure in patients with brain injury

BACKGROUND: The current study investigates the effects of sufentanil on cerebral blood flow velocity and intracranial pressure (ICP) in 30 patients with intracranial hypertension after severe brain trauma (Glasgow coma scale < 6). METHODS: Mechanical ventilation (FIO2 0.25-0.4) was adjusted to maintain arterial carbon dioxide tensions of 28-30 mmHg. Continuous infusion of midazolam (200 micrograms/kg/h intravenous) and fentanyl (2 micrograms/kg/h intravenous) was used for sedation. Mean arterial blood pressure (MAP, mmHg) was adjusted using norepinephrine infusion (1-5 micrograms/min). Mean blood flow velocity (Vmean, cm/s) was measured in the middle cerebral artery using a 2-MHz transcranial Doppler sonography system. ICP (mmHg) was measured using an epidural probe. After baseline measurements, a bolus of 3 micrograms/kg sufentanil was injected, and all parameters were continuously recorded for 30 min. The patients were assigned retrospectively to the following groups according to their blood pressure responses to sufentanil: group 1, MAP decrease of less than 10 mmHg, and group 2, MAP decrease of more than 10 mmHg. RESULTS: Heart rate, arterial blood gases, and esophageal temperature did not change over time in all patients. In 18 patients, MAP did not decrease after sufentanil (group 1). In 12 patients, sufentanil decreased MAP > 10 mmHg from baseline despite norepinephrine infusion (group 2). ICP was constant in patients with maintained MAP (group 1) but was significantly increased in patients with decreased MAP. Vmean did not change with sufentanil injection regardless of changes in MAP. CONCLUSIONS: The current data show that sufentanil (3 micrograms/kg intravenous) has no significant effect on middle cerebral artery blood flow velocity and ICP in patients with brain injury, intracranial hypertension, and controlled MAP. However, transient increases in ICP without changes in middle cerebral artery blood flow velocity may occur concomitant with decreases in MAP. This suggests that increases in ICP seen with sufentanil may be due to autoregulatory decreases in cerebral vascular resistance secondary to systemic hypotension.     

Effect of sudden decompression on tissue pressure in the brain and the cerebrospinal fluid pressure

Extracranial hypertension was produced in cats by means of epidural compression with a baloon. After 2 hours of compression sudden decompression was performed and tissue pressure was compared at symmetrical sites of cerebral hemispheres with cerebrospinal fluid pressure measured in the cisterna magna. It was found that symmetrical tissue pystem, which was due probably to early oedema developing in the compressed area.     

Intracranial pressure and cerebral perfusion pressure in clinically normal equine neonates

Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were determined in 8 clinically normal neonatal foals. After the foals oriented themselves and nursed the mares, they were sedated as necessary, and local anesthesia was provided for making the skin incisions. Using a technique similar to that used in human beings, an indwelling subdural catheter was placed to measure ICP. Carotid artery catheterization was used to measure arterial blood pressure. Cerebral perfusion pressure was calculated as the difference between mean arterial blood pressure and ICP. Intracranial pressure and CPP readings were taken twice during each 24-hour period, starting at 6 hours of age and continuing through 72 hours of age. Mean (+/- SD) ICP were 5.83 +/- 1.82, 8.81 +/- 2.06, and 9.55 +/- 1.55 mm of Hg (range, 2 to 15 mm of Hg), and mean CPP were 80.19 +/- 10.34, 75.30 +/- 10.86, and 76.80 +/- 12.59 mm of Hg (range, 50 to 109 mm of Hg) for each of the first three 24-hour periods after birth, respectively. All 8 foals had physical and neurologic examinations, CSF analysis, and computerized axial tomography evaluations. The foals manifested normal behavior during the interval of measurements, and adverse effects of the procedure were not detected during the monitoring period. Establishment of normal values for ICP and CPP are important to clinicians who have the opportunity to apply this technique for monitoring and evaluating neonatal foals with signs of CNS dysfunction.     

Monitoring of cerebrospinal fluid pressure during embolization of AVM

We experienced that therapeutic embolization of a large cerebral arteriovenous malformation (AVM) led to venous outflow obstruction resulting in intracranial hypertension in a patient who had undergone external decompression. To evaluate hemodynamic changes after embolization, we monitored the cerebrospinal fluid pressure in the next four patients who underwent endovascular treatment. The embolization of a medium AVM resulted in a slight increase in the cerebrospinal fluid pressure. In two medium AVMs, embolization produced slight decreases in the cerebrospinal fluid pressure. In a small AVM, we did not observe any changes in the cerebrospinal fluid pressure during the endovascular treatment. We discuss the mechanism of changes in the intracranial pressure after embolization and conclude that monitoring of the cerebrospinal fluid pressure immediately yields useful information for hemodynamic changes during endovascular treatment.     

Effect of altering cerebrospinal fluid pressure on spinal cord blood flow

The outcome of patients with cholesterolosis was compared with that of those with chronic cholecystitis operated on for chronic acalculous biliary pain. A total of 55 patients with acalculous biliary pain with a median symptom duration of 24 (range 6-120) months were investigated by dynamic cholescintigraphy and followed for a median of 24 (range 12-60) months. Thirty-five patients underwent cholecystectomy, of whom 22 had a low gallbladder ejection fraction (under 35 per cent), with symptomatic improvement in 21 of these (P < 0.01). All four patients with a normal ejection fraction (35-50 per cent) improved after cholecystectomy but only four of nine with a high ejection fraction (over 50 per cent) did so. Results of histological examination were available in 32 patients and revealed cholesterolosis in 20. A low ejection fraction was found in 16 patients with cholesterolosis, of whom 15 showed symptomatic improvement after cholecystectomy; the other four patients had a high fraction and all improved after cholecystectomy. Overall, symptoms in 19 of 20 patients with cholesterolosis improved after cholecystectomy compared with only seven of 12 with chronic cholecystitis (P = 0.03).     

Bulging fontanelle as presenting sign in cystic fibrosis. Vitamin A metabolism and effect on cerebrospinal fluid pressure

A 51/2-month-old infant had the single problem of a bulging fontanelle. A diagnosis of cystic fibrosis with secondary hypovitaminosis A was made by the findings of high sweat chloride values and a low serum carotene level. A greatly accelerated rate of weight gain following the addition of pancreatic enzyme supplements confirmed the presence of malabsorption. The infant developed characteristic fibrosis pulmonary disease at 20 months of age. Animal studies have shown vitamin A deficiency to be associated with increased cerebrospinal fluid (CSF) pressure, diminished absorption of CSF, and pathological findings of thickening and infiltration with mucopolysaccharides of the dura mater around the arachnoid villi.     

Effects of auditory stimuli on intracranial pressure and cerebral perfusion pressure in traumatic brain injury

In the kidney, ischaemia-reperfusion results in both hypoxic and oxidant cellular injury which is most marked in the tubules of cortex and outer medulla. These contrasting conditions may have opposite effects on the expression of enzymes that reduce or repair oxidant damage. To investigate this, the activities of CuZn and Mn superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) were measured after 4 h and 3, 6, and 10 days of reperfusion following sham surgery or 45- or 90-min left renal artery occlusion. The right kidney served as internal control. Sham surgery had no effect on Mn SOD or GPx, but caused small (p < 0.05) reductions in CuZn SOD and GST activities. Forty-five minutes of ischaemia had no net effect on Mn SOD, increased GPx activity (maximum at 6 days, p < 0.01), and reduced CuZn SOD (nadir 3 days, p < 0.02) and GST (nadir 6 days, p < 0.02) activities. Ninety minutes of ischaemia again had no net effect on Mn SOD, prevented the induction of GPx, and further suppressed the activities of CuZn SOD and GST. The activity of the non-anti-oxidant enzyme lactate dehydrogenase was equal in left and right kidneys after 45 min of ischaemia, but different (p < 0.01) 10 days following 90-min injury, due to a combination of reduced activity in the ischaemic kidney and an increase of activity in the internal control. The immediate effect of ischaemia-reperfusion injury on the kidney is to reduce the activity of intracellular anti-oxidant enzymes in proportion to the severity of the ischaemic insult. Recovery or net induction of enzyme activity paralleled tubular regeneration. Protection resulting in acquired resistance to a second ischaemic event is unlikely to be due to induction of anti-oxidant enzymes if it occurs within 6 days.     

Aldosterone secretion during high sodium cerebrospinal fluid perfusion of the brain ventricles

Conscious sheep with permanent indwelling cannulae in the lateral ventricles and the cisterna magna were Na depleted and then perfused for 9 h with an artificial CSF solution. There were 3 experimental groups: Group I (n=5) received perfusion with aritifical CSF containing NA 170 MEq./1, Group II (n=7) received perfusion with artificial CSF containing Na 145 mEq./1, Group III (n=7) received no perfusion. In Group I the blood aldosterone level fell from 26.4 +/- 7.4 to 8.6 +/- 2.3 ng/100 ml by 9 h after perfusion. There was no significant change in plasma [Na] or [K], blood angiotensin II or plasma renin concentration. Blood cortisol and corticosterone levels rose. There was also a fall in post-perfusion. Group III showed no significant change in blood aldosterone concentration. Multivariate statistical analysis showed that the fall in aldosterone levels during 170 mEq./l Na perfusion could not be accounted for by changes, either alone or together, of ACTH as evidenced by alteration in blood cortisol or corticosterone, or by change of plasma [Na], [K] or renin concentrations. This data supports the hypothesis of an additional factor which may be of CNS origin being involved in the control of aldosterone secretion.     

The influence of changes in arterial CO2 and blood pressure on the collateral circulation and the regional perfusion pressure in monkeys with occlusion of the middle cerebral artery

In 7 baboons and 5 macaques the effects of hypercapnia, hypocapnia, hypertension, and combinations of hypertension plus hypocapnia and of hypertension plus hypercapnia on the regional perfusion pressure (rPP) in the brain area rendered ischaemic by occlusion of the middle cerebral artery (MCA) were studied. A new technique for recording the pressure in the occluded MCA was used. The regional tissure pressure (rTP) was recorded with the so called wick type pressure transducers. Hypercapnia produced a marked decrease in rPP in the ischaemic brain area. Hypertension, especially in combination with hypocapnia, produced a very pronounced increase in rPP in the ischaemic brain area. The clinical implications of these findings are discussed. Occlusion of the homolateral common carotid artery (CCA) was followed by a very slight and transient drop in the occluded MCA pressure. Occlusion of the occluded MCA pressure.     

Influence of urapidil on cerebrospinal fluid pressure in humans with uncompromised intracranial compliance

OBJECTIVE: Determine the influence of urapidil on mean lumbar cerebrospinal fluid pressure (CSFP), mean arterial pressure (MAP), mean central venous pressure (CVP) and heart rate (HR) in awake humans without any evidence of cerebral or cardiovascular disease. DESIGN: Open, single-dose volunteer study. INTERVENTIONS: CSFP was measured via a spinal needle after i.v. injection of a single dose of 0.2 mg kg-1 urapidil in six volunteers (2 female, 4 male). MEASUREMENTS AND RESULTS: After administration of urapidil, CSFP increased from 7 +/- 1 mmHg to 10 +/- 1 mmHg (p < 0.05), MAP decreased from 88 +/- 7 mmHg to 74 +/- 5 mmHg (p < 0.05), CPP decreased from 81 +/- 7 mmHg to 64 +/- 5 mmHg (p < 0.05) and CVP decreased from 0 +/- 1 mmHg to -3 +/- 1 mmHg (p < 0.05). CONCLUSION: Our data suggest that in humans with presumed normal intracranial compliance the administration of urapidil causes a small but statistically significant increase in CSFP due to a parallel decrease in MAP.     

The peripheral effect of fentanyl on postoperative pain

The clinical value of the analgesic effect of opioids administered peripherally (except for intraarticular administration) has not been clearly demonstrated. The aim of this study was to test the hypothesis that fentanyl, added to a local anesthetic for wound infiltration, can enhance postoperative analgesia via a peripheral mechanism. Patients with inguinal herniorrhaphy performed under spinal anesthesia were randomly assigned to one of two groups (n = 10 each). At the end of surgery, the wound was infiltrated with 10 mL of lidocaine 0.5% and fentanyl 0.001% (10 microg) in one group; in the other group, the wound was infiltrated with 10 mL of lidocaine 0.5% alone (and fentanyl 10 microg IM contralaterally). The following variables were determined in a double-blind manner: the duration of anesthesia (response to a von Frey filament), the duration of analgesia (time to mild postoperative pain), postoperative meperidine consumption, intensity visual analog scale of spontaneous and movement-associated pain 24 h after surgery, and wound pain threshold 24 h after surgery (pressure algometry). The addition of fentanyl for wound infiltration enhanced the duration of anesthesia (130+/-37 vs 197+/-27 min; P < 0.001) and decreased the intensity of spontaneous (50+/-17 vs 19+/-18 mm; P < 0.002) and movement-associated (56+/-15 vs 26+/-21 mm; P < 0.002) pain 24 h postoperatively. Differences between groups for other variables were not statistically significant. Fentanyl added to a local anesthetic for wound infiltration after spinal anesthesia can enhance postoperative analgesia by a peripheral mechanism. IMPLICATIONS: Fentanyl can enhance analgesia by a peripheral mechanism. Added to a local anesthetic for wound infiltration, it may be of benefit for the relief of postoperative pain.     

Regional cerebral blood flow and cerebrospinal fluid amino acid analysis in elderly dementia

Regional cerebral blood flow and amino acid concentration in the cerebrospinal fluid were studied in 12 cases of vascular dementia, 12 cases of Alzheimer's disease, 12 cases of chronic alcoholism, and 12 age-matched healthy controls. In vascular dementia, blood flows were decreased in the cerebral cortex, frontal white matter, thalamus, caudate nucleus, and putamen and alpha-aminobutyric acid and glutamic acid concentrations were increased in the cerebrospinal fluid. In Alzheimer's disease, blood flows were decreased in the frontal cortex, parietal cortex, temporal cortex, and frontal white matter and alanine concentration was increased in the cerebrospinal fluid. In chronic alcoholism, blood flows were decreased in the cerebral cortex, thalamus, and putamen and urea, alanine, and glycine concentrations were increased in the cerebrospinal fluid.     

The effect of high pressure insertion and antibiotic inclusions upon the mechanical properties of polymethylmethacrylate

The properties of self-curing polymethylmethacrylate as affected by the admixing of an antibiotic to the powder-liquid mixture and as affected by insertion technique demonstrated that the antibiotic agent may leach from the surface of the acrylic, but not necessarily from the interior. The compressive and tensile strength, determined on two different commercial formulations, suggests that the antibiotic additive is not detrimental to the mechanical properties. A high pressure insertion technique produces a significant improvement in the mechanical properties of the self-curing acrylic material.