- Email: [email protected]
UNPREDICTABLE SPINAL ANAESTHESIA
152
BRITISH JOURNAL OF ANAESTHESIA
Sir,—Dr Alston's findings show that plain and hyperbaric bupivacaine produce equally predictable levels of sensory block when given intrathecally to the seated patient [1]. Our study showed that predictability may be obtained with lumbar puncture in the lateral position without unacceptably high blocks [2]. Many practitioners find the lateral position more convenient, especially in patients with restricted mobility, rather than sitting and maintaining that position for 2 min as recommended by Dr Alston. Clearly, both techniques may be used as appropriate to achieve the desired effect. J. BANNISTER
Dundee REFERENCES
EXTRADURAL SOMATOSTATIN Sir,—The report by Desborough and colleagues [1] of the use of extradural somatostatin in postoperative pain was read with some concern. Currently there is a body of peer-reviewed literature which suggests that somatostatin 1-14 administered spinally in three different species may have an irreversible, deleterious effect on spinal tissue [2-7] at doses less than those which produce analgesia. Animal studies might be deemed sufficiently different (multiple dosing, higher concentration, intrathecal route) as not to be relevant to human studies. I could accept this rationale if the mechanisms of toxicity were known, and excluded in humans. Indeed, I should be enthusiastic about a blinded, well-controlled study such as that reported by these authors, particularly as it confirmed the behavioural relevance of animal models which also failed to detect an analgesic effect of spinal somatostatin 1-14. However, without information to the contrary regarding mechanisms of toxicity, I wonder why an Institutional Hospital Ethics Committee approved a drug for which the side effects were not documented and for which the use is not indicated exclusively (as, for example, the use of a potentially lethal chemotherapeutic agent in cancer) in a population of healthy patients, and what information had been conveyed to the patient in the informed consent? I do not think that one may place reliance on previous uncontrolled clinical studies, which themselves proceeded in man without the benefit of knowledge of mechanism, as being supportive of continued human investigation. A tmnll additional query relates to the nature of the molecule used, its vehicle and source. Somatostatin is the name given to a family of peptides that range from 14 to 28 amino acids and have different properties. These peptides may be diluted with salts and other products from the synthesis and therefore, the source and vehicle should be quoted. T. L. YAKSH
San Ditgo
Sir,—Our study was carried out between July 1987 and April 1988 after Ethics Committee approval was granted on July 20, 1987. None of the publications concerning neurotoxicity were available before our submission to the Ethics Committee or during the study. The Ethics Committee and the patients were informed that somatostatin had been given by the extradural and inrrathecal route in human studies and had been reported to be effective in the treatment of acute and chronic pain without side effects. The study proceeded with the full knowledge and support of Serono U.K., the suppliers of the somatostatin 1-14 which was a freeze-dried, lyophilizcd preparation diluted in 0.9 % sodium chloride. We agree that the studies quoted by Professor Yaksh deal with neurotoxicity resulting from intrathecal administration of somatostatin in different species and cannot be related directly to human studies using extradural somatostatin. None of the patients in our study suffered any neurological sequelae. However, we pointed out in our discussion the more recent work by Gauman and Yaksh [1] and Mollenholt and colleagues [2] and we stated "possible toxic effects suggest that its further use in clinical practice is unjustifiable". J. DESBOROUGH
London REFERENCES 1. Gauman DM, Yaksh TL. Intrathecal somatostatin in rats: antinociception only in the presence of toxic effects. Anesthesiology 1988; 68: 733-732. 2. Mollenholt P, Post C, Rawal N, Freedman J, Hokfelt T, Paulsson I. Antinociceptive and neurotoxic actions of somatostatin in rat spinal cord after intrathecal administration. Pain 1988; 32: 95-105.
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on July 15, 2015
1. Alston RP. Spinal anaesthesia with 0.5% bupivacaine 3 ml: comparison of plain and hyperbaric solutions administered to seated patients. British Journal of Anaesthesia 1988; 61: 385-389. 2. Bannister J, McClure JH, Wildsmith JAW. Effect of glucose concentration on the intrathecal spread of 0.5 % bupivacine. British Journal of Anaesthesia 1990; 64: 232-234.
REFERENCES 1. Desborough JP, Edlin SA, Burrin JM, Bloom SR, Morgan M, Hall GM. Hormonal and metabolic responses to cholecystectomy: comparison of extradural somatostatin and diamorphine. British Journal of Anaesthesia 1989; 63: 508-515. 2. Ackerman E, Chrubasik J, Weinstock M, Wunsch E. Effects of intrathecal somatostatin on pain threshold in rats. Schmerz Pain Douleur 1985; 2: 41-42. 3. Gauman DM, Yaksh TL. Intrathecal somatostatin in rats: antinociception only in the presence of toxic effects. Anesthesiology 1988; 68: 733-732. 4. Gauman DM, Yaksh TL, Post C, Wilcox GL, Rodriguez M. Intrathecal somatostatin in cat and mouse. Studies on pain, motor behavior and histopathology. Anesthesia and Analgesia 1989; 68: 623-632. 5. Gauman DM, Grabow TS, Yaksh TL, Casey SJ, Rodriguez M. Intrathecal somatostatin, somatostatin analogs, substance P analog and dynorphin cause comparable neurotoxicity in rats. Neurosdence 1990; (in press). 6. Long JB, Martinez-Arizala A, Kraimer JM, Holaday JW. Intrathecal somatostatin causes hindlimb paralysis and reduces spinal cord blood flow in rats. Society for Neurosdence 1987; 13: 1309. 7. Mollenholt P, Post C, Rawal N, Freedman J, Hokfelt T, Paulsson I. Antinociceptive and neurotoxic actions of somatostatin in rat spinal cord after intrathecal administration. Pain 1988; 32: 95-105.
BRITISH JOURNAL OF ANAESTHESIA
Sir,—Dr Alston's findings show that plain and hyperbaric bupivacaine produce equally predictable levels of sensory block when given intrathecally to the seated patient [1]. Our study showed that predictability may be obtained with lumbar puncture in the lateral position without unacceptably high blocks [2]. Many practitioners find the lateral position more convenient, especially in patients with restricted mobility, rather than sitting and maintaining that position for 2 min as recommended by Dr Alston. Clearly, both techniques may be used as appropriate to achieve the desired effect. J. BANNISTER
Dundee REFERENCES
EXTRADURAL SOMATOSTATIN Sir,—The report by Desborough and colleagues [1] of the use of extradural somatostatin in postoperative pain was read with some concern. Currently there is a body of peer-reviewed literature which suggests that somatostatin 1-14 administered spinally in three different species may have an irreversible, deleterious effect on spinal tissue [2-7] at doses less than those which produce analgesia. Animal studies might be deemed sufficiently different (multiple dosing, higher concentration, intrathecal route) as not to be relevant to human studies. I could accept this rationale if the mechanisms of toxicity were known, and excluded in humans. Indeed, I should be enthusiastic about a blinded, well-controlled study such as that reported by these authors, particularly as it confirmed the behavioural relevance of animal models which also failed to detect an analgesic effect of spinal somatostatin 1-14. However, without information to the contrary regarding mechanisms of toxicity, I wonder why an Institutional Hospital Ethics Committee approved a drug for which the side effects were not documented and for which the use is not indicated exclusively (as, for example, the use of a potentially lethal chemotherapeutic agent in cancer) in a population of healthy patients, and what information had been conveyed to the patient in the informed consent? I do not think that one may place reliance on previous uncontrolled clinical studies, which themselves proceeded in man without the benefit of knowledge of mechanism, as being supportive of continued human investigation. A tmnll additional query relates to the nature of the molecule used, its vehicle and source. Somatostatin is the name given to a family of peptides that range from 14 to 28 amino acids and have different properties. These peptides may be diluted with salts and other products from the synthesis and therefore, the source and vehicle should be quoted. T. L. YAKSH
San Ditgo
Sir,—Our study was carried out between July 1987 and April 1988 after Ethics Committee approval was granted on July 20, 1987. None of the publications concerning neurotoxicity were available before our submission to the Ethics Committee or during the study. The Ethics Committee and the patients were informed that somatostatin had been given by the extradural and inrrathecal route in human studies and had been reported to be effective in the treatment of acute and chronic pain without side effects. The study proceeded with the full knowledge and support of Serono U.K., the suppliers of the somatostatin 1-14 which was a freeze-dried, lyophilizcd preparation diluted in 0.9 % sodium chloride. We agree that the studies quoted by Professor Yaksh deal with neurotoxicity resulting from intrathecal administration of somatostatin in different species and cannot be related directly to human studies using extradural somatostatin. None of the patients in our study suffered any neurological sequelae. However, we pointed out in our discussion the more recent work by Gauman and Yaksh [1] and Mollenholt and colleagues [2] and we stated "possible toxic effects suggest that its further use in clinical practice is unjustifiable". J. DESBOROUGH
London REFERENCES 1. Gauman DM, Yaksh TL. Intrathecal somatostatin in rats: antinociception only in the presence of toxic effects. Anesthesiology 1988; 68: 733-732. 2. Mollenholt P, Post C, Rawal N, Freedman J, Hokfelt T, Paulsson I. Antinociceptive and neurotoxic actions of somatostatin in rat spinal cord after intrathecal administration. Pain 1988; 32: 95-105.
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on July 15, 2015
1. Alston RP. Spinal anaesthesia with 0.5% bupivacaine 3 ml: comparison of plain and hyperbaric solutions administered to seated patients. British Journal of Anaesthesia 1988; 61: 385-389. 2. Bannister J, McClure JH, Wildsmith JAW. Effect of glucose concentration on the intrathecal spread of 0.5 % bupivacine. British Journal of Anaesthesia 1990; 64: 232-234.
REFERENCES 1. Desborough JP, Edlin SA, Burrin JM, Bloom SR, Morgan M, Hall GM. Hormonal and metabolic responses to cholecystectomy: comparison of extradural somatostatin and diamorphine. British Journal of Anaesthesia 1989; 63: 508-515. 2. Ackerman E, Chrubasik J, Weinstock M, Wunsch E. Effects of intrathecal somatostatin on pain threshold in rats. Schmerz Pain Douleur 1985; 2: 41-42. 3. Gauman DM, Yaksh TL. Intrathecal somatostatin in rats: antinociception only in the presence of toxic effects. Anesthesiology 1988; 68: 733-732. 4. Gauman DM, Yaksh TL, Post C, Wilcox GL, Rodriguez M. Intrathecal somatostatin in cat and mouse. Studies on pain, motor behavior and histopathology. Anesthesia and Analgesia 1989; 68: 623-632. 5. Gauman DM, Grabow TS, Yaksh TL, Casey SJ, Rodriguez M. Intrathecal somatostatin, somatostatin analogs, substance P analog and dynorphin cause comparable neurotoxicity in rats. Neurosdence 1990; (in press). 6. Long JB, Martinez-Arizala A, Kraimer JM, Holaday JW. Intrathecal somatostatin causes hindlimb paralysis and reduces spinal cord blood flow in rats. Society for Neurosdence 1987; 13: 1309. 7. Mollenholt P, Post C, Rawal N, Freedman J, Hokfelt T, Paulsson I. Antinociceptive and neurotoxic actions of somatostatin in rat spinal cord after intrathecal administration. Pain 1988; 32: 95-105.