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GDNF rescues nonpeptidergic unmyelinated primary afferents in streptozotocin-treated diabetic mice.

Sensory deficits induced by diabetes commonly affect small unmyelinated peptidergic and nonpeptidergic sensory neurons. The peptidergic population responds to nerve growth factor (NGF), while the nonpeptidergic DRG neurons postnatally switch their dependency from NGF to glial cell line-derived neurotrophic factor (GDNF). Recent studies have demonstrated that deficient NGF support of peptidergic nociceptors is involved in problems with small-fiber diabetic neuropathy. To determine if nonpeptidergic GDNF-responsive neurons are similarly affected by hyperglycemia, diabetes was induced in mice using streptozotocin (STZ). Four weeks following diabetes induction, staining of axon terminals of nonpeptidergic unmyelinated neurons labeled with the isolectin IB4 or enzyme activity for thiamine monophosphatase (TMP) was reduced in lamina IIi of the lumbar dorsal horn, particularly in the medial region which receives distal sciatic afferents. In contrast, NGF-responsive CGRP-immunoreactive (ir) axons showed no or only a slight decrease in spinal terminations. Insulin treatment in diabetic mice failed to improve deficits in IB4/TMP central afferents. To test whether GDNF or NGF could restore spinal deficits in nonpeptidergic afferents, STZ-treated mice were treated intrathecally for 2 weeks with NGF or GDNF. NGF administration enhanced CGRP-ir staining but failed to improve IB4/TMP projections. GDNF treatment had no effect on CGRP-ir projections but restored TMP labeling in lamina IIi. Our results demonstrate that nonpeptidergic unmyelinated sensory neurons are vulnerable to diabetes and that GDNF administration can selectively reverse deficits caused by diabetes in the IB4/TMP subpopulation.

Animals↗

Implanted pump systems for treatment of spasticity.

In about one third of patients with violent spasticity due to spinal trauma, multiple sclerosis, and diffuse brain injury adequate control with oral antispastic medication cannot be achieved and successful rehabilitation is severely handicapped. In the past these patients were subjected to destructive chemical procedures or extensive surgery. The authors present the results of management of uncontrollable spasticity by means of continuous intrathecal administration of baclofen with a totally implantable gas driven pump system (Infusaid). 30 patients were treated between June 1985 and January. 1987. The main indication was incapacitating spasticity resistant to oral treatment with baclofen and caused by spinal cord injury or lesion (11 patients), multiple sclerosis (11 patients), infantile cerebral palsy (3 patients) and cerebral injury, hypoxia or ischaemia (5 patients). Clinical assessment included spasticity scores, integrated electromyography (Iemg) and motography. Effective control for spasticity with mean reduction of Iemg by 55%, decrease of Ashworth's score from 3 to 0 and improvement of life quality was obtained in all patients with daily dose of 10-800 micrograms of Baclofen. Voluntary resting motoricity was not impaired and there were no untoward central side effects. The excellent effect of intrathecal baclofen in comparison with oral therapy is explained by local, spinal GABAergic inhibitory action of the drug which is delivered directly into spinal subarachnoid space. Dose finding and dose adjustment is performed prior to pump implantation by intermittent injections into a subcutaneous port. The complications of the procedure were minor (catheter displacement, disconnection) and easily correctable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Intrathecal misplacement of an interscalene plexus catheter].

For perioperative anesthesia in a case of shoulder arthroscopy, a continuous interscalene plexus block according to Meier was performed in a 51-year-old female patient. The catheter was placed after stimulator-assisted punction and application of a local anesthetic. A few minutes after a further dose of local anesthetic was given via the catheter, the patient had to be intubated and ventilated with signs of total spinal anesthesia. The cervical CT showed the intrathecal displacement of the catheter, reaching the spinal canal near the root of the 7th spinal nerve. Blind advancement and deep placement increase the risk of an abnormal catheter position. Intraspinal misplacement should be reliably excluded.

Anesthesia, Spinal↗

Spinal biopharmaceutics of bupivacaine and lidocaine by microdialysis after their simultaneous administration in rabbits.

The aim of the present study was to determine the intrathecal bioavailability of a mixture of lidocaine and bupivacaine in a rabbit model of spinal anesthesia by using the microdialysis technique. Catheter and microdialysis probe were inserted under control of the view either in the epidural or in the intrathecal space. First, the epidural disposition of the mixture of bupivacaine and lidocaine was studied after epidural administration. Then, the intrathecal and plasma dispositions of bupivacaine and lidocaine were investigated following intrathecal or epidural administration. The epidural clearance of bupivacaine was higher than that of lidocaine, suggesting a more significant uptake of bupivacaine into the systemic circulation and/or into the CSF. The intrathecal bioavailability of bupivacaine and lidocaine was 12.3 and 17.9%, respectively, while it was 5.5 and 17.7% following the separate administration of each agent [Clément, R., Malinovsky, J.M., Le Corre, P., Dollo, G., Chevanne, F., Le Verge, R., 1999. Cerebrospinal fluid bioavailability and pharmacokinetics of bupivacaine and lidocaine following intrathecal and epidural administrations in rabbits using microdialysis. J. Pharmacol. Exp. Ther. 289, 1015-21]. After intrathecal administration, a decrease in C(max) and AUC values was observed for bupivacaine in comparison with the separate administration. Moreover, after epidural administration, the systemic resorption was slower and lower, especially for bupivacaine. Such a reduction in the systemic absorption of bupivacaine might increase its intrathecal bioavailability, resulting from a vasoconstrictor effect of lidocaine reducing the systemic absorption of bupivacaine from the epidural space leading to an increase of its extent of absorption through meninges into CSF although its absorption rate was not modified.

Anesthesia, Spinal↗

Spinal anaesthesia for spinal surgery.

Spinal anaesthesia for spinal surgery is becoming increasingly more popular because this anaesthetic technique allows the patient to self-position and avoid neurological injury that may occur with prone positioning under general anaesthesia. Spinal anaesthesia reduces intraoperative surgical blood loss, improves perioperative haemodynamic stability and reduces pain in the immediate postoperative period. This leads to a reduced need for analgesics and a reduction in the incidence of nausea and vomiting in the postoperative setting. Spinal anaesthesia for lumbar spine surgery also decreases the incidence of lower extremity thrombo-embolic complications and does not increase the occurrence of problems with micturition. These benefits increase the patient's satisfaction, and they expedite discharge of the patient from the hospital. Combination anaesthetic techniques, using both subarachnoid and epidural dosing schemes, may be beneficial for improving postoperative pain control and add further to the benefit of spinal anaesthesia for lumbar spine surgical procedures.

Anesthesia, Spinal↗

Total knee replacement: a comparison of ropivacaine and bupivacaine in combined femoral and sciatic block.

BACKGROUND: Femoral and sciatic nerve block may improve post-operative analgesia following total knee replacement. OBJECTIVES: To compare the post-operative analgesia following primary total knee replacement provided by spinal anaesthesia alone or in combination with femoral and sciatic nerve block with bupivacaine or ropivacaine. METHODS: Seventy-five patients were randomised into one of three groups: spinal anaesthesia only; spinal anaesthesia and combined femoral and sciatic nerve block with 1 mg x kg(-1) bupivacaine 7.5 mg x ml(-1) to each nerve; spinal anaesthesia and combined femoral and sciatic nerve block with 1 mg x kg(-1) ropivacaine 7.5 mg x ml(-1) to each nerve. RESULTS: The mean (SD) time to first morphine request was significantly prolonged for both groups receiving combined femoral and sciatic block, 912 (489) min for the bupivacaine group and 781 (394) min for the ropivacaine group (P<0.001) compared with 413 (208) min for the group receiving spinal anaesthesia alone. Morphine consumption was significantly reduced in both groups receiving combined femoral and sciatic block. There were no systemic or neurological sequelae in any of the groups. CONCLUSIONS: Femoral and sciatic blockade following intrathecal bupivacaine/diamorphine provided superior analgesia when compared with intrathecal bupivacaine/diamorphine alone. There were no significant clinical differences between the group receiving bupivacaine 7.5 mg x ml(-1) and the group receiving ropivacaine 7.5 mg x ml(-1).

Adult↗

[Influence of positioning on the quality of unilateral spinal anesthesia].

OBJECTIVE: Unilateral spinal anaesthesia ("hemi-spinal") is theoretically associated with the advantages of fewer cardiovascular effects and longer duration of action while offering high density motor block of the extremity affected. METHODS: In a prospective, randomised study 60 patients received 2 mls of 4 % hyperbaric mepivacaine intrathecally. Group I (n = 30) was returned into the supine position after 5 minutes in the lateral position, Group II (n = 30) was kept in the lateral position for 15 minutes. Spread and subsequently offset of sensory and motor block were assessed separately for each side at predetermined time intervals pre-, intra-, and postoperatively. RESULTS: Both groups were identical regarding their morphometric parameters. In Group I (5 minutes), the mean cephalad spread of sensory block of the initially dependent side was T6 after 15 mins and T4 after 25 mins. On the initially non-dependent side, the sensory block reached to T5 after 25 mins. In Group II (15 mins), the initial mean difference was equivalent to two segments (T7/T9). After 25 minutes there was no difference to the results in Group I. CONCLUSIONS: Unilateral spinal anaesthesia ("hemi-spinal") is an attractive concept, supposed to be associated with the above mentioned advantages and the additional benefit of a partially maintained sensation of one limb. The results demonstrated in this study seriously question this theoretical concept. The most likely reason for the lack of inter-lateral differences in sensory block is the high concentration of hyperbaric local anaesthetic in the cerebrospinal fluid on the dependent side, which, on turning the patient to the supine position, will transit to the previously non-dependent side subsequently leading to a significant block.

Anesthesia, Spinal↗

Intrathecal fentanyl with small-dose dilute bupivacaine: better anesthesia without prolonging recovery.

UNLABELLED: Recent concern regarding lidocaine neurotoxicity has prompted efforts to find alternatives to lidocaine spinal anesthesia. Small-dose dilute bupivacaine spinal anesthesia yields a comparably rapid recovery profile but may provide insufficient anesthesia. By exploiting the synergism between intrathecal opioids and local anesthetics, it may be possible to augment the spinal anesthesia without prolonging recovery. Fifty patients undergoing ambulatory surgical arthroscopy were randomized into two groups receiving spinal anesthesia with 3 ml 0.17% bupivacaine in 2.66% dextrose without (Group I) or with (Group II) the addition of 10 microg fentanyl. Median block levels reached T7 and T8, respectively (P = not significant [NS]). Mean times to two-segment regression, S2 regression, time out of bed, time to urination, and time to discharge were 53 vs 67 min (P < 0.01), 120 vs 146 min (P < 0.05), 146 vs 163 min (P = NS), 169 vs 177 min (P = NS), and 187 vs 195 min (P = NS) respectively. Motor blockade was similar between groups, but sensory blockade was significantly more intense in Group II (P < 0.01). Six of 25 blocks failed in Group I, whereas none failed in Group II. The addition of 10 microg fentanyl to spinal anesthesia with dilute small-dose bupivacaine intensifies and increases the duration of sensory blockade without increasing the intensity of motor blockade or prolonging recovery to micturition or street fitness. IMPLICATIONS: Concerns about the neurotoxicity of lidocaine have prompted efforts to find alternatives to lidocaine spinal anesthesia. We studied 50 patients undergoing ambulatory surgical arthroscopy and found that although small-dose bupivacaine alone is inadequate for this procedure, the addition of fentanyl makes it reliable.

Adult↗

Determination of the effective therapeutic dose of intrathecal sufentanil for extracorporeal shock wave lithotripsy.

UNLABELLED: Intrathecal (IT) sufentanil provides effective analgesia for extracorporeal shock wave lithotripsy. However, the optimal dose of sufentanil has not been established. We designed a prospective, randomized, double-blinded study to determine the optimal dose of IT sufentanil. Sixty men were randomized to receive 12.5,15,17.5, or 20 microg of IT sufentanil (n = 15 for each group) via a combined spinal epidural technique. Inadequate analgesia was treated with IV propofol, and the epidural was activated for a pain score greater than 6 on a 10-point verbal analog pain scale. Intraoperative and postoperative visual analog pain scale scores were significantly higher in the 12.5-microg group compared with 20-microg group (3.2 +/- 1.6 vs 1.6 +/- 1.2, P < 0.05, and 1.1 +/- 0.5 vs. 0.5 +/- 0.4, P < 0.05, respectively). The smaller-dosage groups of IT sufentanil required significantly more supplemental boluses of propofol compared with the 20-microg group (67%, 53%, and 40% vs 6%, respectively, P < 0.05). However, pruritus was significantly diminished in the smaller-dosage groups compared with the 20-microg group (55%, 60%, and 67% vs 100%, P < 0.05). The time to discharge was significantly shorter in the 15-microg group compared with the 20-microg group (84 +/- 40 min vs 126 +/- 48 min, P < 0.05). These results suggest that 15 microg of IT sufentanil may be the optimal IT dose for patients undergoing extracorporeal shock wave lithotripsy. IMPLICATIONS: Many anesthetic techniques are used for extracorporeal shock wave lithotripsy (ESWL). We have previously shown that intrathecal sufentanil was effective for ESWL, but was associated with a high incidence of itching. We tested 60 patients in four spinal sufentanil dose groups and found that doses of 15 and 17.5 microg provided the most effective analgesia with the fewest side effects for ESWL, with only mild itching.

Adolescent↗

Pharmacokinetic aspects of intrathecal morphine analgesia.

Fifteen patients undergoing thoracotomy were given 0.25 or 0.50 mg morphine intrathecally (L2-L3 or L3-L4) for an analgetic and pharmacokinetic study. Administration of morphine at the end of the operation resulted in a highly variable duration of analgesia ranging from 1-20.5 and 1-40 h for the 0.25 and 0.50 mg groups, respectively. Calculation of cumulative consumption pattern of additional analgesics given im indicated a dose-related analgesia lasting around 12 h. Morphine concentrations in the CSF were high and dose dependent. Thus, at 1 h, CSF concentrations (means +/- SEM) were 4,228 +/- 361 ng/ml and 10,447 +/- 1,538 ng/ml for the 0.25 and 0.50-mg groups, respectively. The plasma concentrations generally were very low, i.e., under 1 ng/ml. For the 0.50 and 0.25 mg groups, the terminal elimination half-life in CSF was 175 +/- 9 min and 196 +/- 13 min, respectively: the volume of CSF distribution was 0.88 +/- 0.16 ml X kg-1 and 1.06 +/- 0.17 ml X kg-1, respectively: and the clearance from CSF was 2.81 +/- 0.41 microliter X kg-1 X min-1 and 3.41 +/- 0.55 microliter X kg-1 X min-1, respectively (means +/- SEM). The study indicates that the significant pharmacokinetic parameter related to the long duration of analgesia after intrathecal morphine administration probably is the high CSF concentrations found, since the rate of elimination from CSF is similar to what is reported for morphine in plasma. Furthermore, modulation of nociceptive input in the thoracic region also may be achieved by lumbar administration, but a slower onset should be anticipated.

Aged↗

The addition of 7.5% glucose does not alter the neurotoxicity of 5% lidocaine administered intrathecally in the rat.

BACKGROUND: Recent reports of major and minor neurologic sequelae after spinal anesthesia have generated concern regarding the safety of some currently used intrathecal agents. The role of glucose, if any, in neurotoxic injury associated with spinal anesthesia is not known. The current experiments sought to determine whether the presence of 7.5% glucose alters the neurotoxicity of intrathecally administered 5% lidocaine. METHODS: Two experiments were performed. First, 48 rats were implanted with an intrathecal catheter and randomly divided into eight equal groups. Each animal received a single intrathecal infusion of 5% lidocaine (groups P1-P4) or 5% lidocaine with 7.5% glucose (G1-G4) for 0.5, 1, 2, or 4 h at a rate of 1 microliter/min. Sensory function was assessed using the tail-flick test; a deficit was defined as a complete lack of response to the heat stimulus at the proximal, mid or distal portion of the tail persisting 4 days after the infusion. In the second experiment, 60 rats were randomly divided into two groups to receive a 1-h intrathecal infusion of 5% lidocaine or 5% lidocaine with 7.5% glucose. Animals were evaluated for increase in the latency of the tail-flick reflex 4 days after infusion. RESULTS: In the first experiment, the two lidocaine solutions produced similar dose-dependent loss of sensory function. In the second experiment, the two solutions induced similar alterations in tail-flick latency. CONCLUSIONS: The presence of 7.5% glucose does not affect the potential of intrathecally administered 5% lidocaine to induce sensory impairment. These findings provide further support for the hypothesis that recent injuries after spinal anesthesia resulted from a direct neurotoxic effect of the local anesthetic.

Anesthesia, Spinal↗

The critically ill patient and regional anesthesia.

PURPOSE OF REVIEW: The review presents an overview of indications, limitations and practical aspects of regional anesthesia and analgesia in critically ill medical and surgical patients. RECENT FINDINGS: A Medline search from 1966 to 2006 with the search terms regional anesthesia, regional analgesia, critically ill and nerve blocks, as well as a search of the Cochrane Library, revealed no studies specifically designed to evaluate the use of regional anesthesia and analgesia in the intensive care unit setting. The available evidence is limited to case reports, cohort studies and expert opinions, and relies heavily on extrapolation from studies primarily designed to examine intraoperative management of surgical patients in whom an intensive care unit admission was part of the perioperative course. SUMMARY: Regional anesthesia and analgesia in the critically ill can help to improve respiratory function, bowel function, mental status and patient comfort secondary to its opioid-sparing effects. Limitations for the use of regional anesthetic techniques are mainly associated with bleeding risks, hemodynamic side-effects, difficulties in neurologic assessment and the potential of local anesthetic toxicity.

Analgesics, Opioid↗

Intrathecal buprenorphine for postoperative analgesia in the elderly patient.

Ninety patients aged 56-85 years scheduled for suprapubic prostatectomy, randomly received intrathecally either bupivacaine 30 mg (group A, n = 30), bupivacaine 30 mg plus buprenorphine 0.03 mg (group B, n = 30) or bupivacaine 30 mg plus buprenorphine 0.045 mg (group C, n = 30). Prolonged postoperative analgesia, minimal disturbance of consciousness and comfortable breathing were common to the groups that received buprenorphine. The higher concentration of buprenorphine improved the quality and duration of analgesia. The only side effects found in the buprenorphine groups were nausea and vomiting in 11 and 14 patients, respectively, in groups B and C. Our study shows that buprenorphine is an effective analgesic, suitable for the management of postoperative pain in elderly patients.

Aged↗

Intrathecal administration of sameridine to patients subjected to arthroscopic knee joint surgery.

BACKGROUND: Sameridine, a new substance with both local anesthetic and opioid effects, was administered intrathecally for the first time to humans, i.e. in patients subjected to arthroscopic knee joint surgery. METHOD: A dose-escalating (10, 15, 20 and 25 mg), open study was performed in 33 patients. Only two patients were included in the 25 mg group. RESULTS: Sameridine provided good quality of surgical anesthesia in all patients except those receiving 10 mg. The maximum level of sensory block, Th5-Th7, was reached within 30 min with a median duration of 3.6-3.9 h. The motor block was more profound with increasing dose, but never lasted longer than the sensory block. The influence on heart rate and blood pressure was minor and atropine and ephedrine were needed in four patients. No clinically significant ECG-changes were detected and no arrhythmias were recorded. Oxygen saturation and respiratory rate did not decrease in a clinically significant way and were not affected by concomitant morphine given i.v. postoperatively. There were few side-effects, the most frequent being mild pruritus (10/33). CONCLUSION: Sameridine provided clinically adequate anesthesia for the patients receiving the doses of 15, 20 and 25 mg. Further studies are needed to evaluate the substance and it is of great interest to clinically investigate the opioid component with respect to postoperative analgesia.

Adolescent↗