Clinical effect of low-dose ketamine in early postoperative period after caesarean section (meta-analysis)

Shindyapina N.V.; Shifman E.M.; Marshalov D.V.; Kuligin A.V.

doi:https://doi.org/10.17116/anaesthesiology202102119

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BACKGROUND

The effects of perioperative low-dose ketamine in caesarean section are not well understood.

OBJECTIVE

To evaluate the clinical effects of various subanesthetic doses and regimens of intravenous ketamine in early postoperative period after caesarean section.

MATERIAL AND METHODS

Searching in the PubMed, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed until December 31, 2019. Heterogeneity of samples was assessed using chi-square test. I²index was used to assess heterogeneity. Both fixed-effect model and random-effect model were applied to assess the cumulative effect. Continuous results are presented as weighted differences between the means of two groups with 95% confidence intervals (95% CI). Differences in dichotomous variables are represented as relative risk (RR) and 95% CI.

RESULTS

A total of 11 randomized controlled trials with 1243 patients were included. In 120-240 min after surgery, difference in mean pain intensity was 2.43 scores, mean level was lower in the ketamine group [–3.69; –1.18]. After 6-8 hours, mean pain intensity was 1.4 scores lower in the ketamine group [–1.71; –1.10] compared to the control group. After 12 hours, analgesic effect of low-dose ketamine was not confirmed, difference in mean pain intensity was 0.60 [–1.40; 0.21]. Low-doses ketamine reduced the risk of postoperative pruritus by 30-40% (RR 0.64, 95% CI 0.41-0.97), did not affect the incidence of nausea/vomiting (RR 1.0, 95% CI 0.76-1.31) and severity of newborn asphyxia (RR 0.01, 95% CI –0.04-0.06].

CONCLUSION

Low-dose ketamine reduces pain syndrome within 6 hours after caesarean section. Further research is needed to confirm the efficacy and safety of ketamine as a component of multimodal analgesia after abdominal delivery.

Keywords:

ketamine

low doses

clinical effects

cesarean section

meta-analysis

Authors:

Shindyapina N.V.

Razumovsky Saratov State Medical University

Shifman E.M.

Moscow Regional Research and Clinical Institute

SPIN RSCI: 4582-8494
Scopus AuthorID: 6507655298
ResearcherID: AAY-3981-2020
ORCID: 0000-0002-6113-8498

Marshalov D.V.

Razumovsky Saratov State Medical University

Kuligin A.V.

Razumovsky Saratov State Medical University

Received:

30.10.2020

Accepted:

12.12.2020

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References:

Pereira Gomes Morais E, Riera R, Porfírio GJ, Macedo CR, Sarmento Vasconcelos V, de Souza Pedrosa A, Torloni MR. Chewing gum for enhancing early recovery of bowel function after caesarean section. The Cochrane Database of Systematic Reviews. 2016;10(10):CD01156. https://doi.org/10.1002/14651858.CD011562.pub2
Sutton CD, Carvalho B. Optimal pain management after cesarean delivery. Anesthesiology Clinics. 2017;35(1):107-124. https://doi.org/10.1016/j.anclin.2016.09.010
Tornero Tornero C, Fernández Rodríguez LE, Orduña Valls J. Multimodal analgesia and regional anaesthesia. Revista Española de Anestesiología y Reanimación (English Edition). 2017;64(7):401-405. https://doi.org/10.1016/j.redar.2017.01.008
Helander EM, Menard BL, Harmon CM, Homra BK, Allain AV, Bordelon GJ, Wyche MQ, Padnos IW, Lavrova A, Kaye AD. Multimodal analgesia, current concepts, and acute pain considerations. Current Pain and Headache Reports. 2017;21(1):3. https://doi.org/10.1007/s11916-017-0607-y
Lee EN, Lee JH. The effects of low-dose ketamine on acute pain in an emergency setting: a systematic review and meta-analysis. PLoS One. 2016;11(10):e0165461. https://doi.org/10.1371/journal.pone.0165461
Heesen M, Böhmer J, Brinck EC, Kontinen VK, Klöhr S, Rossaint R, Straube S. Intravenous ketamine during spinal and general anaesthesia for caesarean section: systematic review and meta‐analysis. Acta Anaesthesiologica Scandinavica. 2015;59(4):414-426. https://doi.org/10.1111/aas.12468
Shindyapina NV, Marshalov DV, Shifman EM, Kuligin AV. Clinical effects of low-dose ketamine intravenous administration in obstetrics: a systematic review. Vestnik intensivnoj terapii im. A.I. Saltanova. 2020;2:104-121. (In Russ.). https://doi.org/10.21320/1818-474x-2020-2-104-121
Ghazi Saidi K, Hajipour A. Effects of preemptive Ketamine on post-cesarean analgesic requirement. Acta Medica Iranica. 2002:40(2):100-103.
Reza FM, Zahra F, Esmaeel F, Hossein A. Preemptive analgesic effect of ketamine in patients undergoing elective cesarean section. The Clinical Journal of Pain. 2010;26(3):223-226. https://doi.org/10.1097/AJP.0b013e3181bff86d
Menkiti ID, Desalu I, Kushimo OT. Low-dose intravenous ketamine improves postoperative analgesia after caesarean delivery with spinal bupivacaine in African parturients. International Journal of Obstetric Anesthesia. 2012;21(3):217-221. https://doi.org/10.1016/j.ijoa.2012.04.004
Milani F, Haryalchi K, Sharami SH, Faraji R, Asgharnia M, Salamat F. The Effect of Low Dose Ketamine (Preemptive Dose) on Postcesarean Section Pain Relief. Journal of Basic and Clinical Reproductive Sciences. 2014;3(2):97-100. https://doi.org/10.4103/2278-960x.140070
Sen S, Ozmert G, Aydin ON, Baran N, Caliskan E. The persisting analgesic effect of low-dose intravenous ketamine after spinal anaesthesia for caesarean section. European Journal of Anaesthesiology. 2005;22(7): 518-523. https://doi.org/10.1017/s026502150500089x
Zangouei A, Zahraei SAH, Sabertanha A, Nademi A, Golafshan Z, Zangoue M. Effect of low-dose intravenous ketamine on revention of headache after spinal anesthesia in patients undergoing elective cesarean section: A double-blind clinical trial study. Anesthesiology and Pain Medicine. 2019;9(6):e97249. https://doi.org/10.5812/aapm.97249
Bilgen S, Köner O, Türe H, Menda F, Fiçicioğlu C, Aykaç B. Effect of three different doses of ketamine prior to general anaesthesia on postoperative pain following Caesarean delivery: a prospective randomized study. Minerva Anestesiologica. 2012;78(4):442-449. https://doi.org/10.1097/00003643-201106001-00507
Haliloglu M, Ozdemir M, Uzture N, Cenksoy PO, Bakan N. Perioperative low-dose ketamine improves postoperative analgesia following Cesarean delivery with general anesthesia. The Journal of Maternal-Fetal and Neonatal Medicine. 2016;29(6):962-966. https://doi.org/10.3109/14767058.2015.1027190
Bauchat JR, Higgins N, Wojciechowski KG, McCarthy RJ, Toledo P, Wong CA. Low-dose ketamine with multimodal postcesarean delivery analgesia: a randomized controlled trial. International Journal of Obstetric Anesthesia. 2011;20(1):3-9. https://doi.org/10.1097/01.aoa.0000410821.83787.b4
Rahmanian M, Leysi M, Hemmati AA, Mirmohammadkhani M. The effect of low-dose intravenous ketamine on postoperative pain following cesarean section with spinal anesthesia: a randomized clinical trial. Oman Medical Journal. 2015;30(1):11-16. https://doi.org/10.5001/omj.2015.03
Xu Y, Li Y, Huang X, Chen D, She B, Ma D. Single bolus low-dose of ketamine does not prevent postpartum depression: a randomized, double-blind, placebo-controlled, prospective clinical trial. Archives of Gynecology and Obstetrics. 2017;295(5):1167-1174. https://doi.org/10.1007/s00404-017-4334-8
Carvalho B, Butwick AJ. Postcesarean delivery analgesia. Best Practice and Research. Clinical Anaesthesiology. 2017;31(1):69-79. https://doi.org/10.1016/j.bpa.2017.01.003
Newport DJ, Carpenter LL, McDonald WM, Potash JB, Tohen M, Nemeroff CB; APA Council of Research Task Force on Novel Biomarkers and Treatments. Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression. American Journal of Psychiatry. 2015;172(10):950-966. https://doi.org/10.1176/appi.ajp.2015.15040465
Landau R, Bollag L, Ortner C. Chronic pain after childbirth. International Journal of Obstetric Anesthesia. 2013;118(1):143-151. https://doi.org/10.1016/j.ijoa.2013.01.008
Gadsden J, Hart S, Santos AC. Post-cesarean delivery analgesia. Anesthesia and Analgesia. 2005;101(5S):62-69. https://doi.org/10.1213/01.ane.0000177100.08599.c8
Chen HP, Sung WC, Hui YL, Hui CK. Anesthetic management of a repeat cesarean section in a parturient with severe peripartum cardiomyopathy requiring ECMO in a previous pregnancy: a case report. Chang Gung Medical Journal. 2011;34(6 suppl):28-33. https://doi.org/10.1016/s0959-289x(03)00052-9
Mei W, Jin C, Feng L, Zhang Y, Luo A, Zhang C, Tian Y. Bilateral ultrasound-guided transversus abdominis plane block combined with ilioinguinal-iliohypogastric nerve block for cesarean delivery anesthesia. Anesthesia and Analgesia. 2011;113(1):134-137. https://doi.org/10.1213/ane.0b013e31821891e2
Kose EA, Honca M, Dal D, Akinci S. B, Aypar U. Prophylactic ketamine to prevent shivering in parturients undergoing Cesarean delivery during spinal anesthesia. Journal of Clinical Anesthesia. 2013;25(4):275-280. https://doi.org/10.1016/j.jclinane.2012.11.014
Lema GF, Gebremedhn EG, Gebregzi AH, Desta YT, Kassa AA. Efficacy of intravenous tramadol and low-dose ketamine in the prevention of post-spinal anesthesia shivering following cesarean section: a double-blinded, randomized control trial. International Journal of Women’s Health. 2017;9:681-688. https://doi.org/10.2147/ijwh.s139655
Shabana AM, Nasr ES, Moawad HE. Effect of ketamine on intraoperative nausea and vomiting during elective caesarean section under spinal anaesthesia: A placebo-controlled prospective randomized double blinded study. Egyptian Journal of Anaesthesia. 2012;28(2):169-174. https://doi.org/10.1016/j.egja.2012.02.001
Modir H, Moshiri E, Kamali A. Prophylatic efficacy of dexamethasone, ketamine and dexmedetomidine against intra-and postoperative nausea and vomiting under spinal anesthesia. Formosan Journal of Surgery. 2019;52(1):17. https://doi.org/10.4103/fjs.fjs_37_18
Loripoor M, Kazemi M. The effect of ketamine for general anesthesia in caesarean section on postpartum depression. Ginecology and Obstetrics Theme: AB 02 Clinical obstetrics/Sub-Theme: AB 2.1 Antenatal and Postnatal Care. 2018;FCS320. https://doi.org/10.1002/ijgo.12582
Ma JH, Wang SY, Yu HY, Li DY, Luo SC, Zheng SS, Wan LF, Duan KM. Prophylactic use of ketamine reduces postpartum depression in Chinese women undergoing cesarean section. Psychiatry Research. 2019;279:252-258. https://doi.org/10.1016/j.psychres.2019.03.026
Brinck EC, Tiippana E, Heesen M, Bell RF, Straube S, Moore RA, Kontinen V. Perioperative intravenous ketamine for acute postoperative pain in adults. The Cochrane Database of Systematic Reviews. 2018;12(12):CD012033. https://doi.org/10.1002/14651858.cd012033.pub4
Dale O, Somogyi AA, Li Y, Sullivan T, Shavit Y. Does intraoperative ketamine attenuate inflammatory reactivity following surgery? A systematic review and meta-analysis. Anesthesia and Analgesia. 2012;115(4):934-943. https://doi.org/10.1213/ane.0b013e3182662e30
Kudoh A, Takahira Y, Katagai H, Takazawa T. Small-dose ketamine improves the postoperative state of depressed patients. Anesthesia and Analgesia. 2002;95(1):114-118. https://doi.org/10.1097/00000539-200207000-00020
Mashour GA, Ben Abdallah A, Pryor KO, El-Gabalawy R, Vlisides PE, Jacobsohn E, Lenze E, Maybrier HR, Veselis RA, Avidan MS; PODCAST Research Group. Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. British Journal of Anaesthesia. 2018;121(5):1075-1083. https://doi.org/10.1016/j.bja.2018.03.030
Rosenblat JD, Carvalho AF, Li M, Lee Y, Subramanieapillai M, McIntyre RS. Oral Ketamine for Depression: A Systematic Review. The Journal of Clinical Psychiatry. 2019;80(3):18r12475. https://doi.org/10.4088/jcp.18r12475
Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, Murrough JW, Feder A, Sos P, Wang G, Zarate CA Jr, Sanacora G. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. American Journal of Psychiatry. 2018;175(2):150-158. https://doi.org/10.1176/appi.ajp.2017.17040472
Bell RF, Dahl JB, Moore RA, Kalso E. Perioperative ketamine for acute postoperative pain. The Cochrane Database of Systematic Reviews. 2006;(1):CD004603. https://doi.org/10.1002/14651858.cd004603.pub2
Pendi A, Field R, Farhan SD, Eichler M, Bederman SS. Perioperative ketamine for analgesia in spine surgery: a meta-analysis of randomized controlled trials. Spine. 2018;43(5):299-307. https://doi.org/10.1097/brs.0000000000002318
Ye F, Wu Y, Zhou C. Effect of intravenous ketamine for postoperative analgesia in patients undergoing laparoscopic cholecystectomy: a meta-analysis. Medicine. 2017;96(51):e9147. https://doi.org/10.1097/md.0000000000009147
Riddell JM, Trummel JM, Onakpoya IJ. Low-dose ketamine in painful orthopaedic surgery: a systematic review and meta-analysis. British Journal of Anaesthesia. 2019;123(3):325-334. https://doi:10.1016/j.bja.2019.05.043
Michelet D, Hilly J, Skhiri A, Abdat R, Diallo T, Brasher C, Dahmani S. Opioid-sparing effect of ketamine in children: a meta-analysis and trial sequential analysis of published studies. Pediatric Drugs. 2016;18(6): 421-433. https://doi.org/10.1007/s40272-016-0196-y
Dahmani S, Michelet D, Abback PS, Wood C, Brasher C, Nivoche Y, Mantz J. Ketamine for perioperative pain management in children: a meta-analysis of published studies. Paediatric Anaesthesia. 2011;21(6):636-652. https://doi:10.1111/j.1460-9592.2011.03566.x
Suppa E, Valente A, Catarci S, Zanfini BA, Draisci G. A study of low-dose S-ketamine infusion as “preventive” pain treatment for cesarean section with spinal anesthesia: benefits and side effects. Minerva Anestesiologica. 2012;78(7):774-781.