Dose-response relationship of clonidine in tetracaine spinal anesthesia

The study was undertaken to define a dose-response relationship for clonidine in prolonging canine tetracaine spinal anesthesia. Using a randomized blind cross-over design, six mongrel dogs were given subarachnoid injections (1 ml) of the following solutions over an 8-week period: tetracaine 4 mg (control), or tetracaine 4 mg with clonidine in doses of 10, 25, 50, 100, 150, 200, and 300 micrograms. With clonidine doses equal to or exceeding 50 micrograms/ml, motor and sensory blockade were significantly (P less than 0.01) prolonged, when compared to the control times. Analysis of data by second order polynomial regression analysis produced a relationship defined by Y = 23.241 + 1.104(x) - 0.0023(x2) with r2 = 0.92 and P less than 0.001 for sensory blockade and Y = 38.7072 + 1.64425(x) - 0.004125(x2) with r2 = 0.90 and P less than 0.005 for motor blockade. From these curves, a plateau in clonidine dose-response for both sensory blockade and motor blockade occurred at 150 micrograms. The increase in duration of spinal anesthesia with clonidine may be related to a direct post-synaptic alpha 2 adrenoceptor arteriolar effect, a spinal cord pre- or post-synaptic alpha 2 antinociceptive action or supraspinal alpha 2 modulation of nociception. No animals showed evidence of neurologic dysfunction during the study. The authors conclude that a well-defined dose-response relationship exists for clonidine in canine tetracaine spinal anesthesia.     

Spinal cord blood flow following sub-arachnoid lidocaine

Twelve mongrel dogs were randomized into two equal groups. Cervical, thoracic and lumbosacral spinal cord and spinal dural blood flows were measured using the radioactive microsphere technique. Blood flow determinations were made prior to and 20 and 40 minutes following lumbar subarachnoid injection of: two per cent lidocaine (100 mg) or two per cent lidocaine (100 mg) with 1/25,000 epinephrine (200 micrograms). Dogs receiving subarachnoid lidocaine demonstrated a decrease in mean arterial blood pressure of 23 per cent and 14 per cent (p less than 0.05), while dogs receiving lidocaine with epinephrine had a decrease of 38 and 34 per cent (p less than 0.05) at 20 and 40 minutes respectively. Cardiac index was not significantly changed in either group. Lumbar subarachnoid lidocaine (100 mg) produced a rapid regional dural hyperemia (observed at 20 minutes postinjection) and a delayed regional spinal cord hyperemia (observed at 40 minutes postinjection) which were not observed following the addition of epinephrine (200 micrograms).     

Cerebrospinal fluid catecholamine levels and duration of spinal anaesthesia

The effects of catecholamines added to dibucaine on the duration of spinal anaesthesia and cerebrospinal fluid catecholamine levels were studied. Free norepinephrine levels increased from 0.107 ng.ml-1 before anaesthesia to 5.8 ng.ml-1 and 1,238 ng.ml-1 after 1.0 microgram or 100 micrograms norepinephrine had been added to the local anaesthetic. The effects of 2.5 micrograms of either norepinephrine or epinephrine added to dibucaine on the duration of motor blockade and sensory regression time were compared. The duration of both were significantly prolonged by added norepinephrine from 96 +/- 17 min to 193 +/- 20 min (sensory blockade) and from 116 +/- 14 min to 204 +/- 34 min (motor blockade), but were not changed by addition of epinephrine. These data suggest that a 2.5 micrograms dose of norepinephrine is sufficient to prolong the duration of spinal anaesthesia and more effective than the same dose of epinephrine.     

Spinal cord blood flow during spinal anesthesia in dogs: the effects of tetracaine, epinephrine, acute blood loss, and hypercapnia

To examine the effects of subarachnoid tetracaine and epinephrine on spinal cord blood flow (SCBF), lumbar SCBF and cerebral blood flow (CBF) were measured simultaneously by the hydrogen clearance technique in dogs (n = 45) anesthetized with halothane. The lumbar subarachnoid administration of tetracaine, 5 mg dissolved in 1 ml of a 7.5% dextrose solution had no significant effect on either SCBF or CBF for 4 hr even though arterial blood pressure and heart rate decreased significantly. After subarachnoid epinephrine alone (100, 300, and 500 micrograms), SCBF varied widely but did not change significantly with any of the injections, nor did CBF. Responses of SCBF to hypercapnia and to acute blood loss during spinal anesthesia with tetracaine were also examined. Increased PaCO2 (from 35 to 57 mm Hg) increased both SCBF and CBF similarly before and after subarachnoid tetracaine; SCBF increased from 26.8 +/- 9.0 ml X 100 g-1 X min-1 (mean +/- SD) before to 34.2 +/- 13.6 ml X 100 g-1 X min-1 during hypercapnia during spinal anesthesia, which was almost identical to the increase (from 31.5 +/- 8.1 ml X 100 g-1 X min-1 to 39.9 +/- 6.0 ml X 100 g-1 X min-1) before spinal anesthesia. Whereas acute blood loss (approximately 20% of estimated blood volume) during spinal anesthesia with tetracaine caused a 23% reduction of SCBF (P less than 0.05), in the absence of tetracaine SCBF remained unchanged during hemorrhagic hypovolemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spinal cord blood flow following subarachnoid tetracaine

Spinal cord and spinal dural blood flow in the cervical, thoracic and lumbosacral regions were measured in dogs using the radioactive microsphere technique. Measurements were taken before and 20 and 40 minutes after lumbar subarachnoid injection of one of the following: physiologic saline; tetracaine 20 mg or tetracaine 20 mg with epinephrine 200 micrograms. No significant change in spinal cord or spinal dural blood flow occurred following subarachnoid physiologic saline or tetracaine with epinephrine. Dogs receiving subarachnoid tetracaine demonstrated a significant increase in lumbosacral spinal cord, and thoracic and lumbosacral dural blood flow at 20 and 40 minutes following injection. Cervical dural blood flow was significantly increased at 40 minutes after subarachnoid tetracaine. Lumbar subarachnoid tetracaine (20 mg) produces a regional spinal cord and generalized dural hyperemia which is prevented by the addition of epinephrine (200 micrograms).     

Spinal narcotics for postoperative analgesia in total joint arthroplasty. A prospective study.

Sixty patients who were scheduled to have an elective total hip or knee arthroplasty were randomly assigned to one of three groups of twenty patients each before operation with spinal anesthesia. A double-blind technique was used throughout the study. The patients in Group I (control group) received hyperbaric 1 per cent tetracaine with epinephrine as the subarachnoid spinal anesthetic; the patients in Group II (morphine group), hyperbaric 1 per cent tetracaine with epinephrine and a single subarachnoid dose of Duramorph (morphine sulphate), 0.5 milligram; and those in Group III (Dilaudid group), hyperbaric 1 per cent tetracaine with epinephrine and a single subarachnoid dose of Dilaudid (hydromorphone hydrochloride), 0.002 milligram per kilogram of body weight. During the first twenty-four hours after the operation, the patients in Group II and Group III had significantly less pain compared with those in Group I. This was shown by the use of a visual linear-analog pain scale (p less than 0.05), the patients' ratings of the quality of relief of pain (p less than 0.02), and comparative measurements of the pain-altering medications that were used (p less than 0.05). The patients in Group II and Group III did not have any more complications or side effects than those in Group I. There was no significant difference in the quality and duration of analgesia between Group II and Group III.     

The clinical use of small-dose tetracaine spinal anesthesia for transurethral prostatectomy

In a double-blinded study, we compared conventional dose tetracaine (8 mg), small-dose tetracaine (4 mg) with added fentanyl and epinephrine, and small-dose tetracaine (4 mg) with added fentanyl subarachnoid anesthesia. Forty-five patients scheduled for transurethral resection of prostate (TURP) under subarachnoid anesthesia were randomly assigned to Group 1 (8 mg hyperbaric tetracaine), Group 2 (4 mg hyperbaric tetracaine, 10 microg fen-tanyl, and 0.2 mg epinephrine), and Group 3 (4 mg hyperbaric tetracaine, 10 microg fentanyl, and 0.2 mL saline). Evaluations were performed after spinal anesthesia. Subarachnoid block was successful in all patients except one in Group 1, who required general anesthesia by mask. The median peak sensory levels 10 min after the induction of spinal anesthesia in Group 1 was T8, which was significantly higher than Group 2 and Group 3 (P < 0.05). The time of sensory and motor recovery in Group 3 was less than in Groups 1 and 2 (P < 0.05). Hypotension was observed in four patients in Group 1 and none in Groups 2 and 3. We conclude that small-dose 4-mg hyperbaric tetracaine plus 10 microg fentanyl might provide adequate anesthesia and fewer side effects for TURP when compared with the conventional (8 mg) dose. IMPLICATIONS: Small-dose hyperbaric tetracaine (4 mg with 10 microg fentanyl added) may provide adequate anesthesia and fewer side effects for transurethral resection of the prostate.     

Subarachnoid bupivacaine decreases spinal cord blood flow in dogs

Eigtheen mongrel dogs were randomized into two equal groups. Cervical, thoracic and lumbosacral spinal cord and spinal dural blood flows were measured using the radioactive microsphere technique. Blood flow determinations were made prior to, and 20 and 40 minutes following lumbar subarachnoid injection of: (1) 0.4 per cent bupivacaine (20 mg), or (2)0.4 per cent bupivacaine (20 mg) with 1/25,000 epinephrine (200 μg). In dogs given subarachnoid bupivacaine or bupivacaine with epinephrine, the maximum decrease in mean arterial blood pressure (33 per cent) occurred at 40 minutes post-injection. Cardiac index decreased in dogs given subarachnoid bupivacaine (197 ± 11 ml·kg^-1·min^-1 controlvs. 141 ± 19 ml·kg^-1 min^-1 at 40 minutes), while it increased in dogs given bupivacaine with epinephrine (201 ± 11ml·kg^-1·min^-1 - control vs. 252 ± 15 ml · kg^-1 · min^-1 at 40 minutes). Dogs receiving subarachnoid bupivacaine demonstrated a significant decrease in spinal cord blood flow to all regions. Dogs receiving subarachnoid bupivacaine with epinephrine demonstrated a significant decrease in thoracic and lumbosacral spinal cord blood flow; however, cervical cord blood flow remained unchanged. Thoracic and lumbosacral dural blood flows were significantly decreased in both groups following subarachnoid injection. Subarachnoid bupivacaine 0.4 per cent (20 mg) and 0.4 per cent with epinephrine 1/25,000 (200 μg) decrease spinal cord and spinal dural blood flow in dogs.     

Spinal cord blood flow following subarachnoid lidocaine

Twelve mongrel dogs were randomized into two equal groups. Cervical, thoracic and lumbosacral spinal cord and spinal durai blood flows were measured using the radioactive microsphere technique. Blood flow determinations were made prior to and 20 and 40 minutes following lumbar subarachnoid injection of: (I) two per cent lidocaine (100 mg) or (2) two per cent lidocaine (100 mg) with 1/25,000 epinephrine (200 μg). Dogs receiving subarachnoid lidocaine demonstrated a decrease in mean arterial blood pressure of 23 per cent and 14 per cent (p < 0.05), while dogs receiving lidocaine with epinephrine had a decrease of 38 and 34 per cent (p < 0.05) at 20 and40 minutes respectively. Cardiac index was not significantly changed in either group. Lumbar subarachnoid lidocaine (100 mg) produced a rapid regional durai hyperemia (observed at 20 minutes postinjection) and a delayed regional spinal cord hyperemia (observed at 40 minutes postinjection) which were not observed following the addition of epinephrine (200 μg).     

Anaesthetic and postoperative analgesic effects of spinal clonidine as an additive to prilocaine in the transurethral resection of urinary bladder tumours

BACKGROUND AND OBJECTIVE: The alpha 2-adrenoceptor agonist clonidine has potent central antinociceptive properties. The study was designed to investigate the effects of the combined subarachnoid administration of clonidine and prilocaine on spinal block and postoperative analgesia for the transurethral resection of tumours in the urinary bladder. METHODS: The controlled, prospective, double-blind study enrolled 40 patients scheduled for elective transurethral resection of bladder tumours under spinal anaesthesia with prilocaine. Patients were randomly assigned to receive an intrathecal injection of prilocaine 75 mg alone (control group) or in combination with clonidine 75 micrograms. We assessed haemodynamic changes (non-invasive arterial pressure, heart rate), pulse oximetry, the upper level of block, the onset and duration of sensory and motor block, postoperative analgesia and any adverse effects. RESULTS: There were no statistically significant differences in demographic data, heart rate, onset time or the levels of sensory or motor block. Analgesia lasted significantly longer in the clonidine group (498.4 +/- 226.9 versus 187.2 +/- 103.1 min; P < 0.05). The duration of motor block was longer in the clonidine group (165.5 +/- 30.6 min) than in the control group (139.7 +/- 40.4 min; P < 0.05) and the duration of sensory block was also longer in the clonidine group (157.3 +/- 24.5 min) than in the control group (137.2 +/- 31.2 min; P < 0.05). Fewer patients in the recovery room needed metamizol (dipyrone) in the clonidine group (5%) than in the control group (50%). Arterial pressure decreased significantly in the clonidine group 75-135 min after the block. CONCLUSIONS: The addition of clonidine 75 micrograms to prilocaine 75 mg for subarachnoid anaesthesia increased the duration of sensory and motor block and reduced the need for additional postoperative analgesics by providing excellent analgesia for about 8 h during recovery from transurethral resection of bladder tumours.     

Dose-related prolongation of hyperbaric tetracaine spinal anesthesia by clonidine in humans

The effect of clonidine, an alpha 2 agonist, on sensory and motor blockade during spinal anesthesia was studied in 44 ASA physical status I II patients scheduled for orthopedic surgery. The patients were randomly allocated into three groups given 15 mg of 0.5% hyperbaric tetracaine (HT), within group I (N = 14) 1 ml isotonic saline, in group II (N = 15) 0.5 ml saline solution and 0.5 ml clonidine (75 micrograms), and in group III (N = 15) 1 ml clonidine (150 micrograms). Sensory blockade (SB) was evaluated by pinprick and motor blockade (MB) according to Bromage's scale. The level of SB was comparable in the three groups but the duration was different. The 75 micrograms clonidine was associated with 25% prolongation of SB at L2 and 29% prolongation of grade 3 MB Clonidine 150 micrograms prolonged the time of SB at L2 by 72% and grade 3 MB by 96%. Colloid infusion and the decrease in diastolic blood pressure were significantly greater in the clonidine 150 micrograms group compared to group I. A dose related prolongation of spinal anesthesia is demonstrated with clonidine.     

Phanton limb sensation under subarachnoid and epidural analgesia - a comparative clinical study of two hundred cases.

Two hundred patients scheduled for various surgical procedures, under subarachnoid and epidural anaesthesia were divided in two groups of 100 for each technique. Subarachnoid analgesia was obtained with five per cent lidocaine, while epidural analgesia was accomplished with 1.5 per cent or 2 per cent lidocaine with adrenaline. This study shows that phantom sensation is painless and self limiting and that it lasts only for the duration of motor and proprioceptive blockade. It does not require any special treatment except psychotherapy, supplemented if needed by tranquilizers. Patients should be positioned after motor blockade has been established.     

Vasoconstrictors in spinal anesthesia with tetracaine--a comparison of epinephrine and phenylephrine

A randomized double-blind study was conducted in 50 orthopedic patients to determine the effect of epinephrine and phenylephrine on the anesthetic properties of intrathecally administered tetracaine. Two doses of each vasoconstrictor agent were studied: 0.2 mg of epinephrine, 0.3 mg of epinephrine, 1 mg of phenylephrine, and 2 mg of phenylephrine. The results show that both vasoconstrictor agents in the doses used significantly prolong duration of sensory anesthesia and motor blockade produced by the subarachnoid administration of tetracaine. At equipotent doses no differences existed between the ability of epinephrine and phenylephrine to prolong the duration of spinal anesthesia produced by tetracaine.     

Inclusion of epinephrine to hyperbaric tetracaine and the supine position enhance the cephalad spread of spinal anaesthesia compared with hyperbaric teracaine alone in the lithotomy position

BACKGROUND: Intrathecal epinephrine can produce prolongation of duration of spinal anaesthesia by reducing vascular absorption of the local anaesthetics. The patient's positioning can change the cephalad spread of hyperbaric local anaesthetics by affecting the lordosis of the vertebral canal. These factors combined are expected to affect the cephalad spread of sensory block levels. The purpose of this study was to investigate whether combined use of epinephrine with hyperbaric tetracaine in the supine position can enhance the cephalad spread of sensory block levels compared with hyperbaric tetracaine alone in the lithotomy position. METHODS: ASA physical status I or II 48 urological (lithotomy group) and 48 orthopaedic patients (supine group) scheduled to undergo elective surgical procedures in the lithotomy or supine position under spinal anaesthesia were enrolled. Patients in each group were randomly divided into two subgroups to receive intrathecal 10 mg of hyperbaric tetracaine with or without 0.2 mg of epinephrine (Groups L, LE, S, and SE). The extent of sensory blockade was assessed by loss of cold sensation. After achievement of sensory blockade up to T10, the patients in Groups L and LE were immediately placed in the lithotomy position. Patients in Groups S and SE were maintained in the supine position. RESULTS: The highest sensory blockade in the SE Group was on average statistically significantly higher than in the L Group. The mean time taken to the highest sensory blockade in the SE Group was statistically significantly longer than in Groups L and S. Atropine for bradycardia was used more frequently in the SE Group than in the other groups. CONCLUSIONS: Combined use of epinephrine with hyperbaric tetracaine in the supine position can enhance the cephalad spread of sensory block levels compared with hyperbaric tetracaine alone in the lithotomy position.     

Bupivacaine, 0.125 per cent, in obstetric epidural analgesia: experience in three thousand cases.

Bupivacaine, 0.125 per cent, with epinephrine, 1:800,000, was administered to 3,000 women in labor. Administration was in the lumbar epidural space for the purpose of achieving satisfactory analgesia with minimal or no motor paralysis. The usual initial dose of 12.5 mg (mean 13 +/- 2 SD) resulted in good sensory analgesia in 83 per cent of the patients and lasted for about and hour (mean 58 +/- 16 min). The mean total dose used for labor and delivery was 55 +/- 20 mg and the mean dose per hour 23 +/- 13 mg. Satisfactory analgesia for labor and delivery was obtained in 92 per cent of the patients, and in 66 per cent there was no discernible motor blockade. In the 3,000 patients, there was no adverse reaction to bupivacaine or epinephrine. No patient had a total spinal block or neurologic sequelae, and no neonatal depression could be attributed to the anesthetic.     

The effect of subarachnoid epinephrine and phenylephrine on spinal cord blood flow

Eighteen mongrel dogs were divided into three equal groups. Spinal cord and spinal dural blood flow in the cervical, thoracic and lumbosacral regions were measured using the radioactive microsphere technique. Measurements were taken before and 10 and 40 minutes after lumbar subarachnoid injection of one of the following: physiologic saline; epinephrine 200 micrograms or phenylephrine 5 mg. No significant change in spinal cord blood flow occurred in any of the groups, nor was there any difference between the groups. Dogs receiving subarachnoid phenylephrine did demonstrate a significant reduction of thoracic dural blood flow at ten minutes. Dogs receiving intrathecal epinephrine or phenylephrine demonstrated a significant reduction in lumbo-sacral dural blood flow at ten minutes after injection. The reduction in dural blood flow was still evident at 40 minutes in dogs receiving phenylephrine. Subarachnoid epinephrine (200 micrograms) and phenylephrine (5 mg) do not effect spinal cord blood flow but do produce regional dural vasoconstriction.     

Spinal anesthesia with tetracaine--effect of added vasoconstrictors

The effect of adding 0.2 ml of 1:1000 epinephrine or 0.5 ml of 1% phenylephrine to 1.5 ml of 1% tetracaine for spinal anesthesia was assessed in 30 patients in a double-blind study. Phenylephrine but not epinephrine produced a significant prolongation of sensory loss in the T12 dermatome. Both vasoconstrictors produced a significant prolongation of the total duration of sensory and motor blockade. These findings differ from those in previous studies in which lidocaine and bupivacaine were used.     

Comparative effects of intrathecal bupivacaine and tetracaine on analgesia, cardiovascular function and plasma catecholamines

Forty otherwise healthy male patients, scheduled for elective inguinal herniotomy, were randomly allocated to spinal anaesthesia with 3 ml 0.5% hyperbaric tetracaine or bupivacaine under double-blind conditions. The extent of blockade (pin-prick and cold sensation), blood pressure and heart rate and plasma catecholamines were measured before and 5, 10, 15, 20 and 30 min after injection, before skin incision. Cephalad spread of sensory and temperature analgesia was insignificantly higher after tetracaine. The mean time taken to reach maximal spread of analgesia was 22 min in both groups. Mean arterial pressure showed a more pronounced decrease in the tetracaine group (22 vs 12%, P less than 0.009). Heart rate fell slightly and similarly in both groups, while rate-pressure product was significantly lower in the tetracaine group. The correlation between the decrease in mean arterial pressure and the cephalad spread of sensory analgesia was similar in the two groups, suggesting that at identical levels of sensory analgesia changes in blood pressure were similar after tetracaine and bupivacaine. Plasma norepinephrine and epinephrine measurements before spinal puncture and at maximal decrease in mean arterial pressure showed a depressed response to fall in blood pressure in the tetracaine group. It is concluded that spinal anaesthesia with 3 ml hyperbaric 0.5% tetracaine is followed by a more pronounced fall in blood pressure compared to an identical dose of bupivacaine. The more pronounced sympathetic blockade, confirmed by plasma catecholamine measurements, following tetracaine is probably due to a higher cephalad spread of neurogenic blockade, rather than a differential effect on sympathetic nerve fibres.     

Comparison of hyperbaric solutions of bupivacaine and tetracaine during continuous spinal anaesthesia

The aim of this study was to compare two equipotent solutions of hyperbaric bupivacaine and tetracaine in 30 elderly patients undergoing elective hip surgery under continuous spinal anaesthesia. With the patient in the supine position, 2 ml (8 mg) of either hyperbaric solution (density 1.030) were administered in a double-blind and randomized fashion. The median maximum sensory and temperature discrimination levels (T5 and T4) were similar with both solutions. The duration of analgesia was not different (114 +/- 23 min for bupivacaine and 125 +/- 35 min for tetracaine). Thirteen out of fifteen patients receiving bupivacaine and all 15 patients receiving tetracaine had complete motor blockade. The haemodynamic changes and vasopressor requirements were comparable. The plasma catecholamine levels measured at four different times remained unchanged and were not different between the two groups at any time. The authors conclude that, during continuous spinal anaesthesia, equipotent hyperbaric solutions of bupivacaine and tetracaine have similar anaesthetic and haemodynamic effects.     

Subarachnoid clonidine reduces spinal cord blood flow and glucose utilization in conscious rats

The authors investigated the spinal blood flow and metabolic effects of subarachnoid clonidine in conscious rats prepared with chronically implanted subarachnoid catheters. For the blood flow experiments, rats received saline (n = 7) or clonidine 20 nmol (7 micrograms; n = 6), 100 nmol (27 micrograms; n = 5), or 400 nmol (107 micrograms; n = 7) intrathecally. Another group of rats received clonidine 400 nmol intravenously (n = 4). Spinal glucose utilization was measured in rats that received either saline (n = 5) or clonidine 100 nmol (n = 5) intrathecally. Spinal cord blood flow (SCBF) and glucose utilization were measured in five gray and three white matter areas of lumbar spinal cord 15 min after drug administration with the autoradiographic iodo-[14C]-antipyrine and 2-[14C]-deoxyglucose methods, respectively. Physiologic differences between the groups were minor. Rats in the blood flow experiments that received clonidine 100 nmol had a slightly lower arterial PO2 level (70 +/- 1 vs. 82 +/- 3 mmHg; P less than 0.05), whereas those in the glucose utilization group were mildly hypocarbic (PCO2 27 +/- 1 vs. 32 +/- 2 mmHg; P less than 0.01) relative to control animals. Only animals that received 400 nmol clonidine intrathecally had significant analgesia, as assessed by the tail-flick test. One control animal for the metabolism experiments was technically unsatisfactory and was excluded from data analysis. Subarachnoid clonidine reduced both SCBF and glucose utilization. In spinal gray matter, the largest decreases in flow (32-44%; P less than 0.01) occurred with 20 nmol clonidine, whereas flow decreased least (12-27%) with the 400-nmol dose.(ABSTRACT TRUNCATED AT 250 WORDS)