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Tobe M, Suto T, Saito S. The history and progress of local anesthesia: multiple approaches to elongate the action. J Anesth 2018; 32:632-636. [PMID: 29855722 DOI: 10.1007/s00540-018-2514-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 05/23/2018] [Indexed: 12/18/2022]
Abstract
Analgesia and temporary inhibition of motor activity without interfering with central nervous function have been the essential merits of local anesthesia. Local anesthetics originated from cocaine have played a major role in local analgesia. However, the relatively short duration of action of local anesthetics has been a concern in intra- and post-operative analgesia. From the early age of modern local anesthesia, physicians and medical scientists had been struggling to control the active duration of local anesthetics. Such approach includes: development of long-acting local anesthetics, with physical tourniquet techniques, co-administration of other medicines such as vaso-constrictive agents or analgesics, development of mechanical devices to continuously or intermittently administer local anesthetics, and utilization of pharmaceutical drug delivery systems. In this review, the historical sequence of studies that have been performed in an effort to elongate the action of local anesthetics is presented, referring to epoch-making medical and scientific studies.
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Affiliation(s)
- Masaru Tobe
- Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma, 371-8511, Japan.
| | - Takashi Suto
- Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma, 371-8511, Japan
| | - Shigeru Saito
- Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma, 371-8511, Japan
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Swain A, Nag DS, Sahu S, Samaddar DP. Adjuvants to local anesthetics: Current understanding and future trends. World J Clin Cases 2017; 5:307-323. [PMID: 28868303 PMCID: PMC5561500 DOI: 10.12998/wjcc.v5.i8.307] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Revised: 05/03/2017] [Accepted: 05/19/2017] [Indexed: 02/05/2023] Open
Abstract
Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids (dexamethasone), anti-inflammatory agents (parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action (tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability (liposomal, microspheres and cyclodextrin systems) and further studies with other drugs (adenosine, neuromuscular blockers, dextrans).
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Rédua MA, Valadão CA, Duque JC, Balestrero LT. The pre-emptive effect of epidural ketamine on wound sensitivity in horses tested by using von Frey filaments. Vet Anaesth Analg 2016; 29:200-206. [PMID: 28404363 DOI: 10.1046/j.1467-2995.2002.00083.x] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2001] [Accepted: 01/04/2002] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To evaluate the pre-emptive analgesic effect of pre-incisional epidural ketamine. STUDY DESIGN A blinded, randomized experimental study. ANIMALS Sixteen mixed breed mares, 7.6 ± 2.8 years old, weighing 352 ± 32 kg. METHODS In a pilot study, an incision was made on one lateral thigh using a lidocaine block and no further analgesics, and it was verified that the nociceptive threshold was lower on the incised side than nonincised side (p ≤ 0.05), and that von Frey filaments evoked a pain response. The 16 animals were divided into group A (ketamine, n = 9) and B (saline, n = 7). An epidural catheter was inserted 24 hours before the trials. The thigh was shaved bilaterally, and the right side was blocked (incised side) using lidocaine. Twenty-five minutes later, ketamine (A) or saline (B) was administered epidurally. Five minutes later, a 10-cm skin incision was made on the right side, and then sutured. Nociceptive threshold was determined with von Frey filaments at 1, 3, and 5 cm around the incision at 15-minute intervals for 2 hours, then at 4, 6, and 8 hours. Behavioral alterations, heart and respiratory rates were recorded. Nociceptive thresholds from these points were averaged to obtain mean values at each time, converted to a logarithmic scale, and submitted to a nonparametric analysis (Mann-Whitney and one-way repeated measures anova test, p ≤ 0.05). RESULTS After 8 hours, the global range score revealed reduced hyperalgesia (p < 0.01) around the incision in 92% (4.65-4.27) of evaluated intervals in group A (ketamine). There were no significant changes in behavior, heart and respiratory rates. CONCLUSIONS It was concluded that pre-emptive epidural ketamine reduced post-incisional pain in the horse, and that von Frey filaments were able to quantify cutaneous sensitivity after tissue damage. CLINICAL RELEVANCE Epidural ketamine injection can reduce post-incisional sensitivity in the horse.
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Affiliation(s)
- Márcia A Rédua
- Departamento de Clínica e Cirurgia, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista, Jaboticabal, Brazil
| | - Carlos Aa Valadão
- Departamento de Clínica e Cirurgia, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista, Jaboticabal, Brazil.
| | - Juan C Duque
- Departamento de Clínica e Cirurgia, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista, Jaboticabal, Brazil
| | - Lúcia T Balestrero
- Departamento de Clínica e Cirurgia, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista, Jaboticabal, Brazil
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Luczak J, Dickenson AH, Kotlinska-Lemieszek A. The Role of Ketamine, an NMDA Receptor Antagonist, in the Management of Pain. PROGRESS IN PALLIATIVE CARE 2016. [DOI: 10.1080/09699260.1995.11746707] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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van den Berg AA, Ghatge S, Wang S. Loss of resistance to saline reduces responses accompanying spinal needle insertion during institution of 'needle-through-needle' combined spinal-epidural analgesia. Anaesth Intensive Care 2011; 38:1013-7. [PMID: 21226430 DOI: 10.1177/0310057x1003800608] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Normal saline or air is used to identify loss of resistance during identification of the epidural space for combined spinal-epidural analgesia. Following epidural needle placement using air for loss of resistance, up to 80% of parturients move, grimace, vocalise or experience paraesthesia or dysaesthesia during subsequent dural puncture by a spinal needle. We compared the effects of saline versus air for loss of resistance on the occurrence of these subjective and objective responses during thecal penetration. With institutional approval, 55 parturients presenting for labour analgesia were studied. After infiltration of lignocaine at an L2-L5 vertebral interspace, a 17 gauge Tuohy epidural needle attached to a 5 ml loss of resistance syringe containing either saline or air was inserted and advanced until loss of resistance was identified by injection of 3 to 5 ml of content. During subsequent 'needle-through-needle' insertion of a 27 gauge pencil-point spinal needle through the meninges, all subjective and objective patient responses were recorded, as well as each patient's reply to the question "Did you feel that?". The two groups (n = 28, n = 27) were comparable. In those given saline and air respectively, 5 (18%) and 12 (44%) parturients responded to and/or acknowledged having perceived dural puncture (P < 0.005). Overall, 7 and 31 (P < 0.0005) subjective and objective responses occurred during dural puncture in those given saline and air, respectively. The study found that use of saline to determine loss of resistance is associated with fewer patient responses at the moment of thecal penetration during 'needle-through-needle' placement of the spinal needle at combined spinal-epidural analgesia.
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Affiliation(s)
- A A van den Berg
- Department of Anesthesiology, The University of Texas Medical School, Houston, Texas, USA.
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Ayesh EE, Jensen TS, Svensson P. Effects of intra-articular ketamine on pain and somatosensory function in temporomandibular joint arthralgia patients. Pain 2008; 137:286-294. [DOI: 10.1016/j.pain.2007.09.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2007] [Revised: 08/23/2007] [Accepted: 09/05/2007] [Indexed: 12/29/2022]
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Choudhuri AH, Dharmani P, Kumarl N, Prakash A. Comparison of caudal epidural bupivacaine with bupivacaine plus tramadol and bupivacaine plus ketamine for postoperative analgesia in children. Anaesth Intensive Care 2008; 36:174-9. [PMID: 18361007 DOI: 10.1177/0310057x0803600206] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
This study compared the effect of single-dose caudal epidural bupivacaine, bupivacaine plus ketamine and bupivacaine plus tramadol for postoperative pain management in children having surgery for inguinal hernia. Following ethics committee approval and informed parental consent, 75 children ASA PS I and II, between three and nine years of age and scheduled for elective unilateral inguinal hernia repair with general anaesthesia were recruited. The patients were randomly divided into three groups to receive 0.5 ml/kg caudal bupivacaine 0.25% (group B), bupivacaine 0.25% plus tramadol 1 mg/kg (group BT) or bupivacaine 0.25% plus ketamine 0.5 mg/kg (group BK). The injections were performed under general anaesthesia. Mean arterial pressure, heart rate, pulse oximetry, respiratory rate and sedation and pain scores were recorded at defined intervals following recovery from anaesthesia. The groups were similar in age, weight and duration of operation (P >0.05). No patient experienced hypotension, bradycardia or respiratory depression. Duration of analgesia was (mean+/-SD) 6.5+/-4.1 h in group B, 9.2+/-3.9 h in group BK, and 8.5+/-3.1 h in group BT (P <0.05). More patients in group B required supplementary analgesics in the first 24 h (P <0.05). Sedation scores were comparable in all groups. Incidence of emesis and pruritus was similar in all the groups. Caudally administered 0.5 ml/kg bupivacaine 0.25% plus ketamine or bupivacaine 0.25% plus tramadol 1 mg/kg provided significantly longer duration of analgesia without an increase in the adverse effects when compared to bupivacaine alone.
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Affiliation(s)
- A Hom Choudhuri
- Department of Anaesthesiology, Aruna Asaf Ali Government Hospital, Delhi, India
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Akbas M, Titiz TA, Ertugrul F, Akbas H, Melikoglu M. Comparison of the effect of ketamine added to bupivacaine and ropivacaine, on stress hormone levels and the duration of caudal analgesia. Acta Anaesthesiol Scand 2005; 49:1520-6. [PMID: 16223400 DOI: 10.1111/j.1399-6576.2005.00806.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND The aim of this study was to compare bupivacaine 0.25% and ropivacaine 0.2%, singly and in combination with ketamine, for caudal administration in children. Duration of analgesia, the need for other analgesics and the stress response were measured. METHODS Eighty children were randomized into four groups of twenty. The bupivacaine group received bupivacaine 0.25% and the ketamine/bupivacaine group received bupivacaine 0.25% plus 0.5 mg/kg ketamine. The ropivacaine group received ropivacaine 0.2%, and the ketamine/ropivacaine group received ropivacaine 0.2% plus 0.5 mg/kg ketamine. The duration of analgesia and analgesic requirements were recorded for each group, as were peri-operative and post-operative concentrations of the stress hormones insulin, glucose and cortisol. RESULTS Ketamine, added to either bupivacaine or ropivacaine for caudal analgesia, gave a longer duration of analgesia (P < 0.05) than bupivacaine or ropivacaine alone. In all groups, blood insulin concentration was increased, and cortisol concentration reduced. Glucose concentration was significantly increased in all groups (P < 0.05). CONCLUSIONS Ketamine can safely be added to ropivacaine 0.2% or bupivacaine 0.25% for caudal anesthesia in order to prolong duration of analgesia and reduce the need for additional analgesics. Stress hormone levels are partially attenuated.
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Affiliation(s)
- M Akbas
- Department of Anaesthesiology, Akdeniz University Medical Faculty, Antalya, Turkey.
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Richebé P, Rivat C, Rivalan B, Maurette P, Simonnet G. Kétamine à faibles doses : antihyperalgésique, non analgésique. ACTA ACUST UNITED AC 2005; 24:1349-59. [PMID: 16115745 DOI: 10.1016/j.annfar.2005.07.069] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Recent data in animal experiments as in clinical trials have clearly reported that pain modulation is related to an equilibrium between antinociceptive and pronociceptive systems. Therefore, the apparent pain level could not only be a consequence of a nociceptive input increase but could also result from a pain sensitization process. Glutamate, via NMDA receptors, plays a major role in the development of such a neuronal plasticity in the central nervous system, leading to a pain hypersensitivity that could facilitate chronic pain development. By an action on NMDA receptors opioids also induce, in a dose dependent manner, an enhancement of this postoperative hypersensitivity. "Antihyperalgesic" doses of ketamine, an NMDA receptor antagonist, were able to decrease this central sensitization not only in painful animal but also in human volunteers exposed to different pain models, or in the postoperative period. Many studies have reported that ketamine effects are elicited when this drug is administered the following manner: peroperative bolus (0.1 to 0.5 mg/kg), followed by a constant infusion rate (1 to 2 microg/kg per min) during the peroperative period and for 48 to 72 hours after anaesthesia. Those ketamine doses improved postoperative pain management by reducing hyperalgesia due to both surgical trauma and high peroperative opioid doses. This antihyperalgesic action of ketamine also limited the postoperative morphine tolerance leading to a decrease in analgesic consumption and an increase in the analgesia quality.
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Affiliation(s)
- P Richebé
- Département d'anesthésie et de réanimation 3, hôpital Pellegrin, place Amélie-Raba-Léon, 33076 Bordeaux cedex, France
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DeRossi R, Junqueira A, Lopes R, Beretta M. Use of ketamine or lidocaine or in combination for subarachnoid analgesia in goats. Small Rumin Res 2005. [DOI: 10.1016/j.smallrumres.2004.11.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Akbas M, Akbas H, Yegin A, Sahin N, Titiz TA. Comparison of the effects of clonidine and ketamine added to ropivacaine on stress hormone levels and the duration of caudal analgesia. Paediatr Anaesth 2005; 15:580-5. [PMID: 15960642 DOI: 10.1111/j.1460-9592.2005.01506.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND The purpose of this study was to compare the analgesic quality and duration of ropivacaine 0.2% with the addition of clonidine (1 microg.kg(-1)) with that of ropivacaine 0.2% and the addition of ketamine (0.5 mg.kg(-1)) to that of ropivacaine 0.2% and also compare the postoperative cortisol, insulin and glucose concentrations, sampled after induction and 1 h later following caudal administration in children. METHODS According to the randomization, patients in the ropivacaine group (R; n = 25) received ropivacaine 0.2%, 0.75 ml.kg(-1); those in the clonidine group (RC; n = 25) received ropivacaine 0.2% 0.75 ml.kg(-1) plus clonidine 1 microg.kg(-1) and those in the ketamine/ropivacaine group (RK; n = 25) ropivacaine 0.2% 0.75 ml.kg(-1) plus ketamine 0.5 mg.kg(-1) (10 mg.ml(-1) concentration). Drugs were diluted in 0.9% saline (0.75 ml.kg(-1)) and prepared by a staff anesthesiologist not otherwise involved in the study. In all groups, the duration of analgesia, analgesic requirements, sedation and insulin, glucose, cortisol concentrations were recorded and statistically compared. RESULTS There were no significant differences among the three study groups with respect to age, weight or duration of surgery. Caudal administration of clonidine 1 microg.kg(-1) or ketamine 0.5 mg.kg(-1) induced a longer duration of analgesia (P < 0.05) compared with ropivacaine alone. Insulin levels were increased and cortisol reduced in all groups. Glucose concentration was increased in all groups and statistically significant (P < 0.05). CONCLUSIONS Addition of ketamine and clonidine to ropivacaine 0.2% 0.75 ml.kg(-1), when administered caudally in children, prolongs the duration of postoperative analgesia. The need for subsequent postoperative analgesic is also reduced. Caudal analgesia attenuates or allows partial changes to postoperative cortisol, insulin or blood glucose responses to surgery.
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Affiliation(s)
- Mert Akbas
- Department of Anaesthesiology, Akdeniz University Medical Faculty, Antalya, Turkey.
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Joo JD, Jeon YS, Choi JW, In JH, Kim YS, Kang YJ, Kim DW, Lim YG, Kim GH. Dose-Related Prolongation of Ropivacaine Epidural Anesthesia by Epidural Ketamine. Korean J Pain 2005. [DOI: 10.3344/kjp.2005.18.1.39] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Affiliation(s)
- Jin Deok Joo
- Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yeon Su Jeon
- Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jin Woo Choi
- Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jang Hyeok In
- Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yong Shin Kim
- Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yoo Jin Kang
- Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Dae Woo Kim
- Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yong Gul Lim
- Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ghi Hyun Kim
- Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Effects of S(+) ketamine added to bupivacaine for spinal anaesthesia for prostate surgery in elderly patients. Eur J Anaesthesiol 2004. [PMID: 15055891 DOI: 10.1097/00003643-200403000-00005] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVE Intrathecal ketamine as the sole anaesthetic agent has demonstrated a lack of cardiovascular depression that should be of advantage in an elderly population. S(+) ketamine has three-times the analgesic potency of R(-) ketamine and its antinociceptive effects after intrathecal administration in rats are known. We decided to evaluate the effects of intrathecal S(+) ketamine added to a small dose of spinal bupivacaine in elderly patients undergoing transurethral prostate surgery. METHODS Forty males over 60 yr old, scheduled for transurethral prostate resection under spinal anaesthesia, were studied in a prospective, double-blinded, randomized way. Patients were allocated to receive either bupivacaine 10 mg or bupivacaine 7.5 mg combined with S(+) ketamine 0.1 mg kg(-1). Spinal block onset time, maximum sensory level, duration of blockade, haemodynamic variables, postoperative analgesic requirements and adverse events were recorded. RESULTS Onset times of motor and sensory block were shorter in the bupivacaine plus S(+) ketamine group. Incomplete motor block of the lower extremities was seen in 80% of the patients in bupivacaine plus S(+) ketamine group. Duration of complete motor block and spinal analgesia was shorter in the bupivacaine plus S(+) ketamine group. There was no significant difference in arterial pressure. Heart rate decreased after spinal anaesthesia in the bupivacaine plus S(+) ketamine group and was significantly lower until the end of anaesthesia. The incidence of adverse effects was not different between groups. CONCLUSIONS Intrathecal S(+) ketamine administered with a low dose of bupivacaine provides shorter motor and sensory block onset time, shorter duration of action and less motor blockade in elderly males.
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McCartney CJL, Sinha A, Katz J. A Qualitative Systematic Review of the Role of N-Methyl-d-Aspartate Receptor Antagonists in Preventive Analgesia. Anesth Analg 2004; 98:1385-400, table of contents. [PMID: 15105220 DOI: 10.1213/01.ane.0000108501.57073.38] [Citation(s) in RCA: 199] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
UNLABELLED We evaluated in a qualitative systematic review the effect of N-methyl-D-aspartate (NMDA) receptor antagonists on reducing postoperative pain and analgesic consumption beyond the clinical duration of action of the target drug (preventive analgesia). Randomized trials examining the use of an NMDA antagonist in the perioperative period were sought by using a MEDLINE (1966-2003) and EMBASE (1985-2003) search. Reference sections of relevant articles were reviewed, and additional articles were obtained if they evaluated postoperative analgesia after the administration of NMDA antagonists. The primary outcome was a reduction in pain, analgesic consumption, or both in a time period beyond five half-lives of the drug under examination. Secondary outcomes included time to first analgesic request and adverse effects. Forty articles met the inclusion criteria (24 ketamine, 12 dextromethorphan, and 4 magnesium). The evidence in favor of preventive analgesia was strongest in the case of dextromethorphan and ketamine, with 67% and 58%, respectively, of studies demonstrating a reduction in pain, analgesic consumption, or both beyond the clinical duration of action of the drug concerned. None of the four studies examining magnesium demonstrated preventive analgesia. IMPLICATIONS We evaluated, in a qualitative systematic review, the effect of N-methyl D-aspartate antagonists on reducing postoperative pain and analgesic consumption beyond the clinical duration of action of the target drug (preventive analgesia). Dextromethorphan and ketamine were found to have significant immediate and preventive analgesic benefit in 67% and 58% of studies, respectively.
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Affiliation(s)
- Colin J L McCartney
- Department of Anesthesia and Pain Management, Toronto Western Hospital and University of Toronto, Ontario, Canada.
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Dal D, Tetik O, Altunkaya H, Tetik O, Doral MN. The efficacy of intra-articular ketamine for postoperative analgesia in outpatient arthroscopic surgery. Arthroscopy 2004; 20:300-5. [PMID: 15007319 DOI: 10.1016/j.arthro.2003.11.038] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
PURPOSE The purpose of this study was to compare the postoperative analgesic effects of intra-articularly administered ketamine, neostigmine, and bupivacaine after outpatient arthroscopic surgery. TYPE OF STUDY Prospective, randomized, double-blind, clinical study. METHODS In this study, 60 patients undergoing arthroscopic surgery other than ligament reconstruction were evaluated for postoperative pain. Ketamine, neostigmine, and bupivacaine were administered intra-articularly. The period of effective analgesia, recorded in minutes, was measured between time 0 and first usage of patient-controlled anesthesia (PCA) by the patients. The visual analog scale (VAS) was used to describe the pain level of the patient. RESULTS VAS values were lower for the 3 medication groups compared with the placebo at rest and 90 degrees knee flexion. Intra-articular administration of 0.5 mg/kg ketamine provided longer duration of analgesia as defined by the first PCA use time (P <.05). The total amount of pethidine and analgesia time were longer for the 3 medication groups. CONCLUSIONS Our basic finding was reduction in postoperative pain and consumption of adequate analgesic drugs with intra-articular ketamine, bupivacaine, or neostigmine use. We have not seen any psychomimetic side effects, particularly as seen with higher doses or systemic use. This study may conclude that intra-articular administration of ketamine provides long-lasting and effective analgesia, similar to neostigmine but less effective than bupivacaine after knee arthroscopy without any adverse effects. LEVEL OF EVEIDENCE: Level I.
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Affiliation(s)
- Didem Dal
- Department of Anesthesiology and Reanimation, Hacettepe University, Ankara, Turkey
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Xie H, Wang X, Liu G, Wang G. Analgesic effects and pharmacokinetics of a low dose of ketamine preoperatively administered epidurally or intravenously. Clin J Pain 2003; 19:317-22. [PMID: 12966258 DOI: 10.1097/00002508-200309000-00006] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES The aim of this study was to compare the analgesic effects and pharmacokinetics of epidural versus intravenous administration of low doses of ketamine. METHODS 45 patients scheduled for selective gastrectomy were randomly assigned into 3 groups: 0.5mg/kg ketamine administered epidurally (Kepi group), 0.5 mg/kg ketamine administered intravenously (Kiv group), or 10ml normal saline administered epidurally (Ctr group). Analgesic effects were evaluated using Visual Analog Scale (VAS) pain scores at rest, time to first request for analgesic (TFA), and subsequent morphine consumption. The plasma concentration of ketamine was measured with high performance liquid chromatography (HPLC) in the Kepi and Kiv groups. The elimination half-life of ketamine was calculated. RESULTS Patients in the Kepi group had significantly lower VAS pain scores, longer TFA, and lower morphine consumption than patients in the Kiv or Ctr groups. Compared with intravenous administration, epidural administration of ketamine resulted in higher plasma concentrations from 90 minutes to 48 hours after injection, and much longer elimination half-life of ketamine, but a lower maximum plasma concentration of ketamine. CONCLUSION The results suggest that epidural administration of a low dose of ketamine provides more effective analgesic effects as seen post-operatively than intravenous administration. The prolonged half-life and high plasma sustained concentration of epidural ketamine might account for the difference in analgesic effects.
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Affiliation(s)
- Hong Xie
- Department of Neurobiology, State Key Laboratory of Medical Neurobiology, Medical Center of Fudan University, Shanghai, China
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18
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Aldrete JA, Parsloe CP. Original contributions of Latin-Americans to anesthesia. BULLETIN OF ANESTHESIA HISTORY 2002; 20:1, 4-11. [PMID: 12017167 DOI: 10.1016/s1522-8649(02)50001-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Affiliation(s)
- J Antonio Aldrete
- Department of Anesthesiology, University of South Florida, Tampa, USA
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19
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Kirdemir P, Ozkoçak I, Demir T, Gögüş N. Comparison of postoperative analgesic effects of preemptively used epidural ketamine and neostigmine. J Clin Anesth 2000; 12:543-8. [PMID: 11137416 DOI: 10.1016/s0952-8180(00)00216-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
STUDY OBJECTIVE To compare the analgesic and side effects of preemptively used epidural ketamine +bupivacaine, neostigmine +bupivacaine, and bupivacaine alone on postoperative analgesia after major abdominal surgery. DESIGN Randomized, controlled study. SETTING Inpatient anesthesia at the department of surgery of a metropolitan hospital. PATIENTS 30 ASA physical status I, II, and III patients scheduled for abdominal surgery. INTERVENTIONS Group K received 1 mL (50 mg) ketamine and 5 mL (25 mg) bupivacaine epidurally, Group N received 1 mL (0.5 mg) neostigmine and 5 mL (25 mg) bupivacaine epidurally, and Group B received 1 mL saline and 5 mL (25 mg) bupivacaine epidurally 30 minutes before operation. All patients underwent anesthesia induction with thiopental and vecuronium; anesthesia was maintained with isoflorane and vecuronium. For postoperative analgesia, all patients received epidural morphine for 48 hours postoperatively. MEASUREMENTS AND MAIN RESULTS Standard monitoring included: 48 hours of analgesic requirement, visual analog scale (VAS), mean arterial pressure (MAP), and heart rate (HR) in the 1st, 2nd, 6th, 12th, 24th, and 48th hours. Data were analyzed using Kruskall-Wallis and Mann Whitney U tests, with a p < 0.05 considered statistically significant. No significant differences were observed regarding MAP and HR among the groups during the study period. In Group N, VAS was significantly lower than Group K and Group B. The total opioid consumption in Group N was significantly lower than in Groups K and B in the first 48 hours after the operation. CONCLUSIONS Preemptive neostigmine can be a good choice for postoperative analgesia.
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Affiliation(s)
- P Kirdemir
- Department of Anesthesiology and Reanimation, Ankara Numune Hospital, Ankara, Turkey
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20
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Abstract
An overview of the spinal administration of ketamine is presented. Ketamine acts as a noncompetitive antagonist of the NMDA receptor Ca(++ channel pore. This effect provides interesting possibilities in pain therapy. However, there are still contrasting results that seem to be due to a lack of comparative controlled studies. The presence of systemic and neurotoxic effects presently limits clinical use).
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Bennett G, Serafini M, Burchiel K, Buchser E, Classen A, Deer T, Du Pen S, Ferrante FM, Hassenbusch SJ, Lou L, Maeyaert J, Penn R, Portenoy RK, Rauck R, Willis KD, Yaksh T. Evidence-based review of the literature on intrathecal delivery of pain medication. J Pain Symptom Manage 2000; 20:S12-36. [PMID: 10989255 DOI: 10.1016/s0885-3924(00)00204-9] [Citation(s) in RCA: 135] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Evidence-based medicine depends on the existence of controlled clinical trials that establish the safety and efficacy of specific therapeutic techniques. Many interventions in clinical practice have achieved widespread acceptance despite little evidence to support them in the scientific literature; the critical appraisal of these interventions based on accumulating experience is a goal of medicine. To clarify the current state of knowledge concerning the use of various drugs for intraspinal infusion in pain management, an expert panel conducted a thorough review of the published literature. The exhaustive review included 5 different groups of compounds, with morphine and bupivacaine yielding the most citations in the literature. The need for additional large published controlled studies was highlighted by this review, especially for promising agents that have been shown to be safe and efficacious in recent clinical studies.
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Affiliation(s)
- G Bennett
- Department of Neurology, MCP Hahnemann University, Philadelphia, PA, USA
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Abstract
In a prospective, randomised, double-blind clinical study, we studied 32 ASA grade I and II boys aged 18 months to 12 years, scheduled for circumcision under general anaesthesia on an outpatient basis. They were randomly allocated to one of two groups: those in the ropivacaine group received caudal ropivacaine 0.2% 1 ml. kg-1 for postoperative analgesia and those in the ketamine/ropivacaine group received caudal ropivacaine 0.2% 1 ml. kg-1 plus caudal ketamine 0.25 mg.kg-1. Postoperative pain was assessed using a modified 10-cm visual analogue scale and analgesia was administered if the pain score exceeded a value of 3. The median duration of analgesia was significantly longer in the ketamine/ropivacaine group (12 h) than in the ropivacaine group (3 h, p < 0.0001), and subjects in the ropivacaine group required significantly more doses of postoperative analgesia than those in the ketamine/ropivacaine group (p < 0.0001). There were no differences between the groups in the incidence of postoperative nausea, vomiting, sedation, emergence delirium, nightmares, hallucinations, motor block and urinary retention.
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Affiliation(s)
- H M Lee
- Department of Anaesthesiology, Intensive Care & Operating Services, Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Road, Tai Po, New Territories, Hong Kong
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Lauretti GR, Gomes JM, Reis MP, Pereira NL. Low doses of epidural ketamine or neostigmine, but not midazolam, improve morphine analgesia in epidural terminal cancer pain therapy. J Clin Anesth 1999; 11:663-8. [PMID: 10680109 DOI: 10.1016/s0952-8180(99)00122-1] [Citation(s) in RCA: 48] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
STUDY OBJECTIVE To examine analgesia and adverse effects of combination epidural pain therapy consisting of administration of morphine with either low dose of ketamine, neostigmine, or midazolam in terminal cancer pain patients. DESIGN Randomized double-blind study. SETTING Teaching hospital. PATIENTS 48 terminal cancer patients suffering from chronic pain. INTERVENTIONS Patients were randomized to one of four groups (n = 12). The concept of visual analog scale (VAS), which consisted of a 10-cm line with 0 equaling "no pain at all" and 10 equaling "the worst possible pain" was introduced. All patients were taking oral amitriptyline 50 mg at bedtime. Pain was initially treated with epidural morphine 2 mg twice daily (12-hr intervals) to maintain the VAS below 4/10. Afterwards, VAS scores > or = 4/10 at any time were treated by adding the epidural study drug (2 ml), which was administered each morning, just after the 2-mg epidural morphine administration. The control group (CG) received 2 mg of epidural morphine (2 ml). The ketamine group (KG) received 0.2 mg/kg epidural ketamine (2 ml). The neostigmine group (NG) received 100 micrograms epidural neostigmine (2 ml). The midazolam group (MG) received 500 micrograms epidural midazolam (2 ml). Patients received the study drugs on a daily basis. MEASUREMENTS AND MAIN RESULTS Duration of effective analgesia was measured as time from the study drug administration to the first patient's VAS score > or = 4/10 recorded in days. The groups were demographically the same. The VAS pain scores prior to the treatment were also similar among groups. Only the patients in the KG demonstrated lower VAS scores compared to the MG (p = 0.018). Time since the epidural study drug administration until patient complaint of pain VAS > or = 4/10 was higher for both the KG and NG compared to the CG (KG > CG, p = 0.049; NG > CG; p = 0.0163). Only the KG used less epidural morphine compared to the CG during the period of study (25 days) (p = 0.003). CONCLUSION The association of either low-dose epidural ketamine or neostigmine (but not midazolam) to epidural morphine increased the duration of analgesia in the population studied (gt;20 days) compared to the CG and MG (8 to 10 days) when administered in the early stages of terminal cancer pain therapy, without increasing the incidence of adverse effects.
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Affiliation(s)
- G R Lauretti
- Department of Surgery, Orthopedics and Traumatology, Hospital das Clinicas, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil
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Patient-controlled epidural analgesia with morphine or morphine plus ketamine for post-operative pain relief. Eur J Anaesthesiol 1999. [DOI: 10.1097/00003643-199912000-00002] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Marsico F, Nascimento P, de Paula A, Nascimento A, Tendillo F, Criado A, de Segura IG. Epidural injection of ketamine for caudal analgesia in the cow. ACTA ACUST UNITED AC 1999. [DOI: 10.1111/j.1467-2995.1999.tb00182.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Schmid RL, Sandler AN, Katz J. Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain 1999; 82:111-125. [PMID: 10467917 DOI: 10.1016/s0304-3959(99)00044-5] [Citation(s) in RCA: 329] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Ketamine hydrochloride is a well known general anesthetic and short acting analgesic in use for almost 3 decades. The role of the NMDA receptor in the processing of nociceptive input has led naturally to renewed clinical interest in N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine. This paper reviews the use and efficacy of low-dose ketamine in the management of acute postoperative pain. The literature was obtained from a computer search of the MEDLINE database from 1966 through December 1998. Studies were included for review if they were randomized, prospective, controlled, double-blind and reported pain scores. We evaluate the clinical literature and discuss the efficacy of low-dose ketamine in the management of acute postoperative pain when administered alone or in conjunction with other agents via the oral, intramuscular, subcutaneous, intravenous and intraspinal routes. Low-dose ketamine is defined as a bolus dose of less than 2 mg/g when given intramuscularly or less than 1 mg/kg when administered via the intravenous or epidural route. For continuous i.v. administration low-dose ketamine is defined as a rate of < or =20 microg/kg per min. We conclude that ketamine may provide clinicians with a tool to improve postoperative pain management and to reduce opioid related adverse effects. The evidence suggests that low-dose ketamine may play an important role in postoperative pain management when used as an adjunct to local anesthetics, opioids, or other analgesic agents. Further research is required in the following areas: (a) dose-finding studies for ketamine as an adjunct to opioids and local anesthetics (b) efficacy and optimal route of administration (c) the role of S(+)-ketamine; (d) the influence of ketamine on long-term outcome such as chronic pain (e) long-term physical and chemical stability of mixtures containing ketamine (f) spinal toxicity of ketamine and (g) effects of low-dose ketamine on cognitive and memory functioning after surgery.
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Affiliation(s)
- Roger L Schmid
- Acute Pain Research Unit, Department of Anaesthesia, The Toronto Hospital and Mount Sinai Hospital, Toronto, Ontario, Canada Department of Anaesthesia, University of Toronto, Toronto, Ontario, Canada Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada
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Yaksh TL. Regulation of spinal nociceptive processing: where we went when we wandered onto the path marked by the gate. Pain 1999; Suppl 6:S149-S152. [PMID: 10491984 DOI: 10.1016/s0304-3959(99)00149-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
The formalization that represented the Gate Control Hypothesis possessed two defining characteristics. Firstly, it served to integrate the body of literature which suggested that processing of nociceptive information is subject to a dynamic regulation, thereby providing a theoretical framework for processes leading to hyper- as well as hypo-algesia. Secondly, the localization of this gating mechanism was placed decisively in the spinal dorsal horn. Subsequent work reflecting upon the pharmacology of spinal systems has served to emphasize the importance of this spinal regulatory process. The complexity of these spinal systems has led to significant advances in our understanding of the transmitter systems by which these gating systems function. It has had the practical consequence of providing important therapeutic modalities serving to control pain processing which originates from both tissue and nerve injury by drugs which are limited in their distribution to the spinal cord.
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Affiliation(s)
- Tony L Yaksh
- Department of Anesthesiology, University of California, San Diego, CA, USA
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Yaksh TL. Spinal systems and pain processing: development of novel analgesic drugs with mechanistically defined models. Trends Pharmacol Sci 1999; 20:329-37. [PMID: 10431212 DOI: 10.1016/s0165-6147(99)01370-x] [Citation(s) in RCA: 115] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Much research has been undertaken in the field of pain in an attempt to find an effective treatment. Insights into the underlying mechanisms of pain have been gained from studies using preclinical animal models (acute stimuli, post-tissue injury and peripheral nerve injury) and evaluating their similarity with the human condition. In this article, these pain models are summarized and the mechanisms of pain discussed in relation to spinal processing. In the context of this research the therapeutic potential of novel analgesics is highlighted as the future looks forward to the many possibilities that the targeted spinal delivery of drugs can bring.
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Affiliation(s)
- T L Yaksh
- Department of Anesthesiology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0818, USA
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30
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Anderson B, Chojnowska E. Pharmacokinetics and the drugs used in pediatric regional anesthesia. ACTA ACUST UNITED AC 1999. [DOI: 10.1016/s1084-208x(99)80033-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Abstract
The discovery of opioid receptors and the subsequent development of the technique of epidural and intrathecal opioid administration are undoubtedly two of the most significant advances in pain management in recent decades. The use of spinal opioids is widespread and increasing. The technique is used widely to treat intraoperative, postoperative, traumatic, obstetric, chronic, and cancer pain. Newer developments include the increasing use of combined local anesthetics and opioids or nonopioids and also PCEA, particularly in the obstetric population. Meta-analysis of controlled trials has demonstrated improved pulmonary outcome in patients receiving epidural postoperative analgesia. Although rare, respiratory depression continues to be a major problem of the technique. None of the currently available opioids is completely safe; however, extensive international experience has shown that patients receiving spinal opioids for postoperative analgesia can be safely nursed on regular wards, provided that trained personnel and appropriate guidelines are available. The importance of a good acute pain service to provide the safe and effective use of spinal opioids cannot be overemphasized.
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MESH Headings
- Analgesia, Epidural
- Analgesia, Patient-Controlled
- Analgesics, Non-Narcotic/administration & dosage
- Analgesics, Non-Narcotic/adverse effects
- Analgesics, Opioid/administration & dosage
- Analgesics, Opioid/adverse effects
- Anesthetics, Local/administration & dosage
- Anesthetics, Local/adverse effects
- Drug Therapy, Combination
- Humans
- Injections, Spinal
- Pain, Postoperative/prevention & control
- Respiration/drug effects
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Affiliation(s)
- N Rawal
- Department of Anesthesiology and Intensive Care, Orebro Medical Center Hospital, Sweden.
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32
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Comparison of the effects of epidural and intravenous ketamine on the duration of epidural analgesia in children. ACTA ACUST UNITED AC 1998. [DOI: 10.1016/s1366-0071(98)80024-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Gómez de Segura IA, De Rossi R, Santos M, López San-Roman J, Tendillo FJ, San-Roman F. Epidural injection of ketamine for perineal analgesia in the horse. Vet Surg 1998; 27:384-91. [PMID: 9662784 DOI: 10.1111/j.1532-950x.1998.tb00145.x] [Citation(s) in RCA: 79] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To determine the analgesic, sedative, and cardiopulmonary effects of epidural ketamine in the horse. ANIMAL POPULATION Six healthy horses (three males and three females) weighing between 350 and 450 kg. METHODS Three doses of ketamine were selected (0.5, 1, 2 mg/kg). Two months before the beginning of experiments, the carotid artery was exteriorized, and 1 week before experiments began, an epidural catheter was placed percutaneously in all animals with the tip located 12 cm cranially in the midsacrum. One week later, either saline (control) or one of three doses of ketamine was injected epidurally. Each animal received each ketamine dose and saline in random order at 1-week intervals. Ketamine was diluted in saline 0.9% before the experiment, and the volume used was adjusted to horse size and correlated to clinically used volumes. All the animals received a standard noxious stimulus consisting of needle insertion into the skin and deep muscle using a 3-point scale for scoring the response. A second scale was used to score the degree of sedation. The response to a noxious stimulus, the degree of sedation, and arterial blood pressure were assessed at previously determined intervals: before drug and 2, 5, 10, and 15 minutes and every 15 minutes to 210 minutes after ketamine or saline administration. Arterial blood samples were drawn for blood gas analysis before drug and at 15, 30, 60, and 90 minutes. RESULTS All the tested doses of ketamine were effective in producing analgesia of the tail, perineum, and upper hindlimb. Total tail and perineal analgesia times were similar depending on dosage (30 minutes for 0.5 and 1.0 mg/kg and 75 minutes for 2.0 mg/kg). A sedative effect of ketamine was also observed in a dose-response manner with a peak effect between 15 and 30 minutes postadministration. No cardiopulmonary effects were observed with any dose of ketamine. CONCLUSIONS Results indicate that epidurally administered ketamine in the horse produces local spinal and central nervous system effects with analgesia and sedation but minimal cardiopulmonary effects. CLINICAL RELEVANCE Further studies are required to determine whether the analgesia is sufficient for surgery.
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Affiliation(s)
- I A Gómez de Segura
- Servicio de Cirugía Experimental; Hospitales Universitarios La Paz, Madrid, Spain
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Chia YY, Liu K, Liu YC, Chang HC, Wong CS. Adding Ketamine in a Multimodal Patient-Controlled Epidural Regimen Reduces Postoperative Pain and Analgesic Consumption. Anesth Analg 1998. [DOI: 10.1213/00000539-199806000-00021] [Citation(s) in RCA: 48] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Chia YY, Liu K, Liu YC, Chang HC, Wong CS. Adding ketamine in a multimodal patient-controlled epidural regimen reduces postoperative pain and analgesic consumption. Anesth Analg 1998; 86:1245-9. [PMID: 9620513 DOI: 10.1097/00000539-199806000-00021] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
UNLABELLED We designed this double-blind study to evaluate the effect of adding small-dose ketamine in a multimodal regimen of postoperative patient-controlled epidural analgesia (PCEA). Ninety-one patients, ASA physical status I-III, undergoing major surgery, received a standardized general anesthesia and epidural catheterization in an appropriate intervertebral space after surgery. A PCEA device was programmed to deliver a regimen of morphine 0.02 mg/mL, bupivacaine 0.8 mg/mL, and epinephrine 4 microg/mL, with the addition of ketamine 0.4 mg/mL (ketamine, n = 45) or without (control, n = 46). The mean visual analog pain scale (VAS) scores during cough or movement for the first 3 days after surgery were higher in the control group than in the ketamine group (P < 0.05), whereas the mean VAS score at rest for the first 2 days were higher in the control group than in the ketamine group (P < 0.05). Furthermore, patients in the control group consumed more multimodal analgesics than patients in the ketamine group for the first 2 days (P < 0.05). The sedation scores and the incidence of side effects (pruritus, nausea, emesis, sleep deprivation, motor block, and respiration depression) were similar between the two groups. We conclude that adding ketamine 0.4 mg/mL in a multimodal PCEA regimen provides better postoperative pain relief and decreases consumption of analgesics. IMPLICATIONS Many studies have evaluated one or a combination of two analgesics for postoperative pain control, but few have examined a multimodal approach using three or four different epidural analgesics. This study demonstrates an additive analgesic effect when ketamine is added to a multimodal analgesic treatment.
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MESH Headings
- Analgesia, Epidural
- Analgesia, Patient-Controlled
- Analgesics, Opioid/administration & dosage
- Analgesics, Opioid/adverse effects
- Analgesics, Opioid/therapeutic use
- Anesthetics, Dissociative/administration & dosage
- Anesthetics, Dissociative/adverse effects
- Anesthetics, Local/administration & dosage
- Anesthetics, Local/adverse effects
- Bupivacaine/administration & dosage
- Bupivacaine/adverse effects
- Consciousness/drug effects
- Double-Blind Method
- Drug Combinations
- Epinephrine/administration & dosage
- Female
- Humans
- Ketamine/administration & dosage
- Ketamine/adverse effects
- Male
- Middle Aged
- Morphine/administration & dosage
- Morphine/adverse effects
- Morphine/therapeutic use
- Muscle, Skeletal/drug effects
- Nausea/chemically induced
- Pain Measurement
- Pain, Postoperative/prevention & control
- Pruritus/chemically induced
- Respiration/drug effects
- Sleep Wake Disorders/chemically induced
- Vasoconstrictor Agents/administration & dosage
- Vomiting/chemically induced
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Affiliation(s)
- Y Y Chia
- Department of Anesthesia, Veterans General Hospital-Kaohsiung, Taiwan, Republic of China.
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Choe H, Kim JS, Ko SH, Kim DC, Han YJ, Song HS. Epidural Verapamil Reduces Analgesic Consumption After Lower Abdominal Surgery. Anesth Analg 1998. [DOI: 10.1213/00000539-199804000-00020] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Choe H, Kim JS, Ko SH, Kim DC, Han YJ, Song HS. Epidural verapamil reduces analgesic consumption after lower abdominal surgery. Anesth Analg 1998; 86:786-90. [PMID: 9539602 DOI: 10.1097/00000539-199804000-00020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
UNLABELLED In this double-blind study, we administered lumbar epidural bupivacaine or bupivacaine plus verapamil to investigate the possible role of the calcium channel blocker, verapamil, in postoperative pain. One hundred patients (ASA physical class I or II) scheduled for lower abdominal surgery were randomly assigned to one of four groups. Group 1 received 10 mL of 0.5% epidural bupivacaine injected 15 min before incision, followed by 10 mL of epidural normal saline 30 min after incision. Group 2 received 10 mL of epidural normal saline injected before incision, followed by 10 mL of 0.5% epidural bupivacaine 30 min after incision. Group 3 received 10 mL of 0.5% epidural bupivacaine plus 5 mg of verapamil injected before incision, followed by 10 mL of epidural normal saline 30 min after incision. Group 4 received the same drugs as Group 3, in the reverse order. Pain and mood numeric rating scores, sedation scores, Prince Henry scores, patient-controlled cumulative postoperative analgesic consumption, and the incidence of side effects were assessed 2, 6, 12, 24, and 48 h after the operation in each group. Cumulative postoperative analgesic consumption in Groups 3 and 4 was significantly lower (P < 0.05) than that in Groups 1 and 2 24 and 48 h after surgery. There were no differences in the pain, mood, and sedation scores and the incidence of side effects among the four groups. We conclude that epidural verapamil decreases postoperative pain, possibly by interfering with normal sensory processing and by preventing the establishment of central sensitization. IMPLICATIONS Calcium plays an important role in pain physiology at the spinal cord level. We examined the effect of bupivacaine plus verapamil (calcium channel blocker) and of bupivacaine alone. We demonstrated that the combination, administered epidurally, resulted in less postoperative analgesic consumption than bupivacaine alone.
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MESH Headings
- Abdomen/surgery
- Adult
- Affect/drug effects
- Analgesia, Epidural
- Analgesia, Patient-Controlled
- Analgesics/administration & dosage
- Analgesics/therapeutic use
- Analgesics, Opioid/administration & dosage
- Analgesics, Opioid/adverse effects
- Analgesics, Opioid/therapeutic use
- Analysis of Variance
- Anesthetics, Local/administration & dosage
- Anesthetics, Local/adverse effects
- Bupivacaine/administration & dosage
- Bupivacaine/adverse effects
- Calcium Channel Blockers/administration & dosage
- Calcium Channel Blockers/adverse effects
- Calcium Channel Blockers/therapeutic use
- Chi-Square Distribution
- Consciousness/drug effects
- Double-Blind Method
- Follow-Up Studies
- Humans
- Incidence
- Injections, Epidural
- Middle Aged
- Morphine/administration & dosage
- Morphine/adverse effects
- Morphine/therapeutic use
- Pain, Postoperative/physiopathology
- Pain, Postoperative/prevention & control
- Premedication
- Sensation/drug effects
- Sodium Chloride
- Spinal Cord/drug effects
- Spinal Cord/physiopathology
- Verapamil/administration & dosage
- Verapamil/adverse effects
- Verapamil/therapeutic use
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Affiliation(s)
- H Choe
- Department of Anesthesiology, Chonbuk National University Medical School, Chonju, Republic of Korea
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Martin DD, Tranquilli WJ, Olson WA, Thurmon JC, Benson GJ. Hemodynamic effects of epidural ketamine in isoflurane-anesthetized dogs. Vet Surg 1997; 26:505-9. [PMID: 9387217 DOI: 10.1111/j.1532-950x.1997.tb00526.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE The purpose of this study was to determine the hemodynamic effects of epidural ketamine administered during isoflurane anesthesia in dogs. STUDY DESIGN Prospective, single-dose trial. ANIMALS Six healthy dogs (five males, one female) weighing 25.3 +/- 3.88 kg. METHODS Once anesthesia was induced, dogs were maintained at 1.5 times the predetermined, individual minimum alveolar concentration (MAC) of isoflurane. Dogs were instrumented and allowed to stabilize for 30 minutes before baseline measurements were recorded. Injection of 2 mg/kg of ketamine in 1 mL saline/4.5 kg body weight was then performed at the lumbosacral epidural space. Hemodynamic data were recorded at 5, 10, 15, 20, 30, 45, 60, and 75 minutes after epidural ketamine injection. Statistical analysis included an analysis of variance (ANOVA) for repeated measures over time. All data were compared with baseline values. A P < .05 was considered significant. RESULTS Baseline values +/- standard error of the mean (X +/- SEM) for heart rate, mean arterial pressure, mean pulmonary artery pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index, stroke index, systemic vascular resistance, pulmonary vascular resistance, and rate-pressure product were 108 +/- 6 beats/min, 85 +/- 10 mm Hg, 10 +/- 2 mm Hg, 3 +/- 1 mm Hg, 5 +/- 2 mm Hg, 2.3 +/- 0.3 L/min/m2, 21.4 +/- 1.9 mL/beat/m2, 3386 +/- 350 dynes/sec/cm5, 240 +/- 37 dynes/sec/cm5, and 12376 +/- 1988 beats/min x mm Hg. No significant differences were detected from baseline values at any time after ketamine injection. CONCLUSIONS The epidural injection of 2 mg/kg of ketamine is associated with minimal hemodynamic effects during isoflurane anesthesia. CLINICAL RELEVANCE These results suggest that if epidural ketamine is used for analgesia in dogs, it will induce minimal changes in cardiovascular function.
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Affiliation(s)
- D D Martin
- Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, USA
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Doherty TJ, Geiser DR, Rohrbach BW. Effect of high volume epidural morphine, ketamine and butorphanol on halothane minimum alveolar concentration in ponies. Equine Vet J 1997; 29:370-3. [PMID: 9306063 DOI: 10.1111/j.2042-3306.1997.tb03141.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
This study determined the effects of epidurally administered morphine, ketamine and butorphanol on halothane minimum alveolar concentration (MAC) in ponies. Seven ponies were anaesthetised with thiopentone and succinylcholine, intubated and anaesthesia maintained with halothane. Ventilation was controlled and blood pressure was maintained within normal limits. Following the determination of baseline halothane MAC for the pelvic and thoracic limbs the ponies were given morphine (0.1 mg/kg bwt), ketamine (0.8 or 1.2 mg/kg bwt), butorphanol (0.05 mg/kg bwt) or saline, epidurally, to a final volume of 0.15 ml/kg bwt. The halothane MAC for the pelvic and thoracic limbs was redetermined following each treatment. The baseline halothane MAC for the control group was mean +/- s.e. 0.85 +/- 0.02% and no significant change occurred after saline administration. Morphine significantly (P = 0.002) decreased MAC from, mean +/- s.e. 0.90 +/- 0.05% to 0.77 +/- 0.06% in the pelvic limb. Ketamine significantly decreased MAC in the pelvic limb from mean +/- s.e. 0.86 +/- 0.06% to 0.71 +/- 0.04%, and 0.82 +/- 0.03% to 0.71 +/- 0.02%, for the low (P = 0.008) and high dose (P = 0.001), respectively. No significant change in MAC occurred following butorphanol. No treatment reduced halothane MAC for the thoracic limb.
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Affiliation(s)
- T J Doherty
- Department of Large Animal Clinical Sciences, University of Tennessee, College of Veterinary Medicine, Knoxville 37901, USA
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Iida H, Dohi S, Tanahashi T, Watanabe Y, Takenaka M. Spinal conduction block by intrathecal ketamine in dogs. Anesth Analg 1997; 85:106-10. [PMID: 9212131 DOI: 10.1097/00000539-199707000-00019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
In addition to its use for intravenous (I.V.) anesthesia, ketamine can provide pain relief in humans when administered spinally. To elucidate the mechanisms of intrathecal (I.T.) ketamine analgesia, we observed differences in the effects of I.V. and I.T. ketamine on intraspinal evoked potentials (ISEPs) in 28 dogs anesthetized with pentobarbital. Bipolar extradural electrodes were inserted at the cervical and lumbar regions of the spinal cord for recording descending ISEPs represented by the two negative deflections, Waves I and II. I.V. ketamine 2 and 10 mg/ kg did not affect the amplitude and latency of Wave I, whereas the large dose (10 mg/kg) significantly decreased the amplitude but not the latency of Wave II. I.T. ketamine 1 and 5 mg/kg caused significant dose-dependent decreases in both Wave I and II amplitudes and prolongations of both Wave I and II latencies. These I.T. effects on ISEPs are consistent with previous in vitro observations that ketamine blocks axonal conduction. We conclude that axonal conduction block may contribute to the analgesic mechanism of I.T. ketamine.
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Affiliation(s)
- H Iida
- Department of Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, Gifu City, Japan.
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Iida H, Dohi S, Tanahashi T, Watanabe Y, Takenaka M. Spinal Conduction Block by Intrathecal Ketamine in Dogs. Anesth Analg 1997. [DOI: 10.1213/00000539-199707000-00019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Choe H, Choi YS, Kim YH, Ko SH, Choi HG, Han YJ, Song HS. Epidural morphine plus ketamine for upper abdominal surgery: improved analgesia from preincisional versus postincisional administration. Anesth Analg 1997; 84:560-3. [PMID: 9052301 DOI: 10.1097/00000539-199703000-00017] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Increased postoperative pain may be caused by central nervous system plasticity, which may be related to actions of N-methyl-D-aspartic acid (NMDA) receptors on neurons in the dorsal horn of the spinal cord. Opioids act mainly on presynaptic receptors and reduce neurotransmitter release, while ketamine antagonizes NMDA receptors and prevents wind-up and long-term potentiation. Thus, we postulated that central nervous system sensitization would be prevented more effectively by the preoperative use of these two drugs simultaneously, and the effect of preemptive analgesia would be demonstrated. Ketamine, 60 mg, and morphine, 2 mg, were injected epidurally through an indwelling catheter that was inserted at the T7-8 interspace in 60 ASA physical status class 1-2 patients. The drugs were injected before induction of anesthesia (Group 1; n = 30) or immediately after removal of a surgical specimen (Group 2; n = 30). An additional 2 mg of morphine was injected when the patients complained of resting pain. The analgesic effect was assessed by the time from first analgesic injection to second dose and the number of patients who needed supplemental injections. Complications were also noted. The duration of analgesia was longer (P < 0.01) in Group 1 (31.1 +/- 16.0 h) than in Group 2 (21.1 +/- 12.0 h), and the proportion of patients who needed supplemental injections was decreased (P < 0.05) in Group 1 (56.7%) compared with Group 2 (90.0%). The incidence of adverse effects was not different between the two groups. In conclusion, preoperative administration of morphine and ketamine is more effective in reducing postoperative pain than it is when given during the operation.
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Affiliation(s)
- H Choe
- Department of Anesthesiology, Chonbuk National University Medical School, Chonju, Republic of Korea
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Choe H, Choi YS, Kim YH, Ko SH, Choi HG, Han YJ, Song HS. Epidural Morphine Plus Ketamine for Upper Abdominal Surgery. Anesth Analg 1997. [DOI: 10.1213/00000539-199703000-00017] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Aithal H, Pratap AK, Singh G. Clinical effects of epidurally administered ketamine and xylazine in goats. Small Rumin Res 1997. [DOI: 10.1016/s0921-4488(96)00919-4] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Semple D, Findlow D, Aldridge LM, Doyle E. The optimal dose of ketamine for caudal epidural blockade in children. Anaesthesia 1996; 51:1170-2. [PMID: 9038462 DOI: 10.1111/j.1365-2044.1996.tb15063.x] [Citation(s) in RCA: 75] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Sixty boys aged up to 9 years undergoing orchidopexy were randomly allocated to receive one of three solutions for caudal epidural injection: group A received 1 ml.kg-1 of 0.25% bupivacaine with 0.25 mg.kg-1 of preservative-free ketamine, group B received 1 ml.kg-1 of 0.25% bupivacaine with ketamine 0.5 mg.kg-1 and group C received 1 ml.kg-1 of 0.25% bupivacaine with 1 mg.kg-1 of ketamine. Postoperative pain was assessed by means of a modified Objective Pain Score and analgesia was administered if this score exceeded four. The median duration of caudal analgesia was 7.9 h in group A, 11 h in group B and 16.5 h in group C. There were no differences between the groups in the incidence of motor block, urinary retention, postoperative vomiting or postoperative sedation. Group C had a significantly higher incidence of behavioural side effects, including slightly odd behaviour, vacant stares and abnormal effect than groups A and B.
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Affiliation(s)
- D Semple
- Department of Anaesthesia, Royal Hospital for Sick Children, Edinburgh
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Yanli Y, Eren A. The effect of extradural ketamine on onset time and sensory block in extradural anaesthesia with bupivacaine. Anaesthesia 1996; 51:84-6. [PMID: 8669575 DOI: 10.1111/j.1365-2044.1996.tb07662.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
In a randomised, double blind study of 30 patients, we have compared two regimens for extradural anaesthesia: 20 ml bupivacaine 0.5%, 25 mg (0.5 ml) ketamine, 1 in 200,000 adrenaline; and 20 ml bupivacaine 0.5%, 0.5 ml 0.9% saline, 1 in 200,000 adrenaline. The main outcome measures were onset time to acceptable bilateral anaesthesia and postoperative analgesic duration. The time to onset of anaesthesia was reduced by 8 min in the bupivacaine-ketamine group compared with the bupivacaine alone group. In addition, the anaesthetic levels were two segments higher in the bupivacaine-ketamine group (T7 versus T9). Side effects were similar in both groups and there was no significant difference in postoperative analgesic requirements between the two groups. The addition of ketamine to bupivacaine given epidurally appears to be useful in the reduction of onset time to blockade.
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Affiliation(s)
- Y Yanli
- Department of Anaesthesia, Ordu National Hospital, Turkey
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Abstract
Recent research has demonstrated the increasing importance of the spinal cord in processing and modulating nociceptive input. Different groups of drugs, each acting by a unique mechanism, have been shown to block nociceptive afferent transmission. None of the currently available spinally administered local anesthetics, opioids or non-opioids produce analgesia without side effects. Non-opioids such as alpha-2-adrenergic agonists may be more suited as adjuvants rather than sole analgesic agents and their main role lies in reducing the dose requirements of other analgesics. Spinal somatostatin and ketamine may have neurotoxic potential. The role of these drugs and of midazolam in pain management appears to be limited. Preliminary results suggest that the neuropeptide octreotide has potent analgesic effects. 'Balanced spinal analgesia' using a combination of low doses of drugs, with separate but synergistic mechanisms of analgesia, may produce the best results. The optimal drug combinations and dosages remain to be determined. It is essential that animal neurotoxicity studies followed by controlled clinical trials are performed before widespread spinal administration of new drugs.
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Affiliation(s)
- N Rawal
- Department of Anesthesiology and Intensive Care, Orebro Medical Center Hospital, Sweden
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Edwards ND, Fletcher A, Cole JR, Peacock JE. Combined infusions of morphine and ketamine for postoperative pain in elderly patients. Anaesthesia 1993; 48:124-7. [PMID: 8460758 DOI: 10.1111/j.1365-2044.1993.tb06849.x] [Citation(s) in RCA: 66] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
The value of using a combined infusion of morphine with a variable dose of ketamine for postoperative analgesia following upper abdominal surgery was assessed in a double-blind randomised study of 40 elderly patients. Four groups of 10 patients received an infusion of morphine at 1 mg.h-1, either alone, or combined with ketamine at a rate of 5, 10 or 20 mg.h-1. The addition of ketamine to a continuous infusion of morphine did not significantly improve either analgesia or postoperative lung function. Increasing the dose of ketamine resulted in an increased incidence of postoperative dreaming (p < 0.01).
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Affiliation(s)
- N D Edwards
- Department of Anaesthesia, University of Sheffield Medical School
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Abstract
The spinal cord can be affected by several categories of drugs: local anesthetics, opiate agonist, alpha 2 adrenergic agonists, and ketamine. The mechanism of action, side effects, and usefulness of these injections vary with the type of drug used.
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Affiliation(s)
- A M Klide
- Department of Clinical Studies-Philadelphia, University of Pennsylvania School of Veterinary Medicine
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