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Journal of Obstrectic Anaesthesia and Critical Care
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 Table of Contents  
Year : 2019  |  Volume : 9  |  Issue : 2  |  Page : 60-64

Comparison of levobupivacaine alone versus levobupivacaine with ketamine in subcutaneous infiltration for postoperative analgesia in lower segment cesarean section

1 Department of Anaesthesia, AIIMS, Delhi, India
2 Department of Obstetrics, CMCH, Ludhiana, Punjab, India
3 Department of Anaesthesia, DMCH, Ludhiana, Punjab, India
4 Department of Obstetrics, DMCH, Ludhiana, Punjab, India

Date of Submission28-May-2019
Date of Acceptance20-Jun-2019
Date of Web Publication06-Sep-2019

Correspondence Address:
Dr. Paridhi Kaler
56 F, Rishi Nagar, Ludhiana - 141 001, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/joacc.JOACC_25_19

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Context: Local anesthetic wound infiltration is employed as a part of multimodal analgesia to reduce opiate consumption and pain after lower segment cesarean section (LSCS). Additional blockade of pain pathway at spinal level by ketamine prolongs the duration of analgesia. Aims: To compare analgesic efficacy of subcutaneous wound infiltration of levobupivacaine or levobupivacaine plus ketamine following LSCS. Material and Methods: Randomized double blind study was conducted on 60 parturients undergoing LSCS under spinal anesthesia. Group A received surgical wound infiltration with 0.5% levobupivacaine 2 mg/kg body weight and Group B parturients were infiltrated with 0.5% levobupivacaine plus ketamine 1 mg/kg body weight diluted with normal saline. Postoperative pain scores, time to first rescue analgesia (FRA), hemodynamic parameters, and total opioid analgesic consumption were assessed. Results: Pain free period and time to FRA was 1.5 hours later in group B, which also had reduced mean VAS scores. In addition, the overall pain scores and total opioid consumption were significantly less (P = 0.003) in Group B. Only 50% in Group B and 97% parturients in Group A needed rescue analgesia. Patient satisfaction score was statistically superior in Group B (P = 0.009). Incidence of nausea and vomiting was comparable between the groups (P = 0.554). Conclusions: Addition of ketamine to levobupivacaine for surgical wound infiltration prolongs the analgesia duration, improves patient satisfaction, and decreases 24-hour opioid consumption.

Keywords: Levobupivacaine, multimodal analgesia, N-Methyl-D-Aspartate antagonist, opioid consumption, subcutaneous wound infiltration

How to cite this article:
Kaler P, Verma I, Grewal A, Taneja A, Sood D. Comparison of levobupivacaine alone versus levobupivacaine with ketamine in subcutaneous infiltration for postoperative analgesia in lower segment cesarean section. J Obstet Anaesth Crit Care 2019;9:60-4

How to cite this URL:
Kaler P, Verma I, Grewal A, Taneja A, Sood D. Comparison of levobupivacaine alone versus levobupivacaine with ketamine in subcutaneous infiltration for postoperative analgesia in lower segment cesarean section. J Obstet Anaesth Crit Care [serial online] 2019 [cited 2021 Sep 16];9:60-4. Available from: https://www.joacc.com/text.asp?2019/9/2/60/266143

  Introduction Top

Postoperative pain is one of the major concerns during and after cesarean sections.[1] Post cesarean patients have an additional compelling reason to be provided adequate pain relief so that early ambulation helps in breastfeeding and care of the newborn. In addition, mobilization is a key factor in attenuating the risk posed by exaggerated thromboembolic phenomenon in pregnancy.[2] Multimodal analgesia is an established technique for controlling postoperative pain as it combines multiple drugs with different duration of action by different routes of administration thereby reducing the side effects of individual drugs. Various drug combinations administered by different methods such as oral, intramuscular (IM), intravenous (IV), rectal route, and perineural infiltration are used to provide effective and safe analgesia.[3] Local anesthetics, when infiltrated subcutaneously in pain-sensitive planes, block the activation and propagation of action potential in pain fibers which are stimulated by incision and inflammatory mediators. This reduces the generation of afferent impulses and prevents the development of central sensitization.[4],[5]

Among the commonly used local anesthetic agents, levobupivacaine [(2S)-1-butyl-N-(2, 6-dimethylphenyl) piperidine-2-carboxamide], an amino-amide local anesthetic and the pure S (−) enantiomer of bupivacaine, has strongly emerged as a safer alternative to other local anesthetic agents for regional anesthesia with lesser cardiotoxicity and neurotoxicity.[6] Wound infiltration with levobupivacaine has a positive effect on wound healing due to its anti-inflammatory actions during the initial postoperative period and good postoperative analgesia following cesarean section.[7],[8]

Local anesthetic infiltration as an adjunct to regional analgesia and general anesthesia are beneficiary in cesarean section as they reduce opioid consumption.[9],[10] Corsini and Cuvillon studied single-dose 30 ml intraincisional 0.5% levobupivacaine infiltration in women scheduled for cesarean section and concluded that it significantly reduced postoperative opioid consumption.[11] Pain transmission also occurs by sensitization of spinal cord by glutamate and aspartate in N-Methyl-D-Aspartate (NMDA) receptors. Ketamine, an NMDA receptor antagonist, acts by inhibiting NMDA receptors on the postsynaptic membrane of the posterior horn of spinal cord. Thus, it inhibits transmission of pain from the spinal level to the central nervous system and consequently suppresses hyperalgesia and allodynia.[12]

Therefore, we hypothesized that addition of ketamine to levobupivacaine for local wound infiltration would enhance the postoperative analgesic efficacy of levobupivacaine.

  Material and Methods Top

The study was conducted obtaining the Institutional Ethics Committee (IEC) approval as a randomized double blind controlled study on parturients scheduled for elective cesarean section. Written informed consent was obtained from all the parturients before the procedure. This trial was registered with Central Trial Registery - India (CTRI) with reference number CTRI/2017/09/009808.

A total of 60 adult parturients of Physical status II or III as per the American society of anesthesiologists (ASA) without any medical or obstetrical problems, and scheduled for cesarean section under spinal anesthesia were included in this study. Uncooperative, unwilling parturients, and those with history of anaphylaxis to local anesthetics, opioids and/or drugs to be used, current or past history of drug abuse, psychiatric disease with body weight more than 100 Kg, and unable to understand the Visual Analog Scale (VAS) were excluded from the study.

Parturients were randomized to one of the two groups (30 each) according to computer-generated random numbers kept in separate, sealed, and numbered envelopes. Group A parturients received subcutaneous surgical wound infiltration with a solution of 0.5% levobupivacaine at 2 mg/kg body weight (rounded to nearest multiple of 10) to a maximum of 150 mg (maximum safe dose) diluted with normal saline to a total of 32 ml. Group Bparturients received subcutaneous surgical wound infiltration with a solution of 0.5% levobupivacaine 2 mg/kg body weight (rounded to nearest multiple of 10) to a maximum of 150 mg plus ketamine 1 mg/kg body weight diluted with normal saline to a total volume of 32 ml. An anesthetist not involved in the conduct of anesthesia and postoperative management prepared the study drugs and handed over to the surgeon for subcutaneous infiltration prior to skin closure under all aseptic precautions. A blinded observer assessed the postoperative pain relief up to 24 hours after the surgical procedure. A thorough preanesthetic check-up was conducted before the surgery which comprised of detailed history, general physical examination, and systemic examination. Routine investigations (complete hemogram, coagulation profile, random blood sugar) and other investigations if indicated were done prior to surgery. The VAS was shown and the scoring system was explained preoperatively. The parturients were informed before surgery that they can request for an analgesic after surgery if they feel pain and they can choose to withdraw from the study at any time.

After shifting the parturients to the operation theater in left lateral position, prior to subarachnoid block, pulse rate (P.R), noninvasive blood pressure (NIBP), respiratory rate (R.R), oxygen saturation (SpO2), and electrocardiography (ECG) were recorded. These parameters were monitored throughout the procedure and recorded every 10 minutes. An intravenous access was achieved and preloading with 10 ml/kg body weight with balanced salt solution was done. Thereafter, subarachnoid block was given under full aseptic precautions in sitting position. A 26 Gauge Quincke's needle was introduced into the subarachnoid space at L3-4/L4-5 vertebral level. With the needle orifice cephalad and after confirmation of free flow of CSF, 2.0 ml of 0.5% heavy bupivacaine was injected through the spinal needle, which was withdrawn after the injection was given and the parturient was then turned supine. Surgery was allowed to proceed after sensory block was achieved upto level of T4 and motor block to level of modified bromage scale of 3. In case of partial/failed spinal anesthesia, general anesthesia was administered and the parturient was excluded from the study. At the end of surgery, parturients received subcutaneous skin infiltration of the study drug as per random group allocation in a blinded manner by the surgeon prior to skin closure.

Parturients were continuously monitored for heart rate, blood pressure, respiratory rate, and oxygen saturation. Postoperative pain scores and analgesic requirement were recorded along with hemodynamic parameters immediately after shifting to postoperative recovery room at 0 min, 30 mins, 1, 2, 4, 6, 8, 12, 16, 20, and 24 hours, respectively. Postoperatively, all parturients received slow infusion in 100-ml saline of diclofenac sodium 75 mg at 0 min and, thereafter, 8 hourly as part of multimodal postoperative analgesia regimen. Any parturient with VAS greater than or equal to 4 or at any point of time complained of pain was administered with 50 mg intravenous injection of tramadol, a rescue analgesic. Time of first rescue analgesic (FRA) request was noted. If the parturient still reported VAS ≥4 after 1 hour of receiving tramadol, similar doses were repeated up to a maximum of 100 mg in contiguous 4 hours or 400 mg in 24 hours. The total rescue analgesic consumption for the 24 hours after surgery was recorded.

The observer (anesthesia resident posted in postanesthesia care unit) who recorded the postoperative vitals and analgesic consumption was blinded to the group allocation of the parturients to maintain the double blind nature of the study. The outcomes of the parturients were evaluated in terms of quality of pain relief (as assessed by VAS score) and time of FRA administration, number of times rescue analgesic given, and the total consumption volume of analgesic 24 hours postoperatively. Parturients were also evaluated for any adverse effects. The primary outcome, postoperative pain relief was measured using the VAS scale and the total analgesic consumption during the 24 hours postoperative period. The secondary outcome, that is, patient satisfaction score (PSS) was assessed postoperatively at 24 hours and was subjectively graded as:

  • Excellent(4)
  • Good(3)
  • Moderate(2)
  • Poor(1)

Statistical analysis

Data were described in terms of number and percentages. The mean and standard deviation were computed. Comparison of quantitative variables was done using Student t-test. For comparing categorical data, Chi square (χ2) or exact test was performed as applicable. A probability value (P value) of less than 0.05 was considered statistically significant. SPSS version 20.0 was used for all statistical calculations.

  Results Top

We observed that both the groups were comparable with respect to demographic data. The zero hour (baseline) mean heart rates were comparable between groups A and B (P = 0.937). The mean heart rate of group A was higher than that of group B which was statistically insignificant at majority of the time points except at 4th and 6th hour post operative. The intragroup comparison of mean heart rate showed a gradual decrease in values across time in both the groups but was more prominent in group B [Table 1]. Correspondingly, parturients in group A had higher mean VAS scores than those in group B at all time intervals and statistically significant difference were observed at 1, 4, 6, and 12 hours [Table 2]. The mean time to FRA of group A was at 3.29 ± 2.07 hours (197.4 mins) while that of group B was at 4.80 ± 2.24 hours (288 mins). This difference was statistically significant (P = 0.039). Thus, parturients in Group B complained of pain 1.5 hours later than the parturients in group A [Table 3]. In group B with ketamine as an adjuvant to levobupivacaine, only 50% of the parturients demanded rescue analgesia, where as nearly 97% of the parturients needed rescue analgesia in group A which received levobupivacaine alone. [Figure 1] Parturients in group A consumed a mean total opioid dose of 96.55 ± 37.63 mg in 24 hours compared to 63.33 ± 22.89 mg in group B. Thus, statistically significant higher opioid consumption was observed in group A than in group B (P = 0.003, [Table 4]). There were 6% parturient in Group A compared to 23% in Group B in whom the PSS was of excellent quality and 26% in Group A and 46% in Group B graded the PSS with good quality. Thus, the difference in patient satisfaction score was statistically significant between the two groups (P = 0.009, [Figure 2]).
Table 1: Trends in postoperative mean heart rate

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Table 2: Mean VAS scores at various time intervals

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Table 3: Mean time to first rescue analgesia (FRA) and VAS at FRA

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Figure 1: Percentage of parturients requiring rescue analgesic in each group. N – No, Y - Yes

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Table 4: Total rescue analgesic consumption in 24 h (mg)

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Figure 2: Percentage of parturients with patient satisfaction score (PSS)

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  Discussion Top

Subcutaneous wound infiltration with local anesthetics is effective, safe, inexpensive, and without the need for expertise. A systemic review and meta-analysis substantiated the analgesic efficacy of various local anesthetic wound infiltration techniques for postoperative analgesia following cesarean section. They observed a statistically significant reduction in postoperative pain scores and total opioid consumption in 24 hours with local anesthetic wound infiltration.[13] We used levobupivacaine alone and levobupivacaine plus ketamine for local wound infiltration after cesarean section in view of their analgesic and anti-inflammatory properties along with a lesser cardiotoxic profile.

In our study on 60 parturients, none were excluded and both the groups were statistically comparable with respect to age, weight, and ASA grade. We observed that patients in group B (L+K) experienced a postoperatively pain-free period of up to 288 mins where as patients in group A (L) demanded rescue analgesia at 192 mins. This portrays that local wound infiltration provides adequate analgesia and addition of ketamine to levobupivacaine significantly contributes in the prolongation of pain-free period (P = 0.039). Though we observed statistically significant prolonged times to FRA, the mean VAS score at FRA in both the groups was comparable—(4.79 ± 1.11) in group A and 4.47 ± 0.52 in group B). This implies that while levobupivacaine conferred profound analgesic effect in both the groups, addition of ketamine helped in prolonging the time required for FRA. Abdallah et al. evaluated the analgesic efficacy of preincisional infiltration with ketamine or levobupivacaine in 48 patients undergoing abdominal hysterectomy. They observed an increased duration of analgesia for upto 158 mins with ketamine and 127 mins with levobupivacaine (P = 0.001). The time to FRA in their study group using levobupivacaine was shorter compared to our study group A which can be attributed to the use of less volume and concentration of levobupivacaine solution for infiltration, that is, 20 ml and only 0.25% levobupivacaine in their study.[14]

The overall VAS scores of our study were higher in group A with statistically significant higher values at 1, 4, 6, and 12 hours, which correlated with a significant increase in heart rate at 4 and 6 hours in the same group. This translates that the group infiltrated with levobupivacaine alone had comparatively initial peaks of higher pain scores reflected by higher heart rates at the same time of observations, whereas the group which received ketamine as an adjunct to levobupivacaine for infiltration encountered less pain during the same period. Thus, addition of ketamine as an adjunct to levobupivacaine enhances its efficacy in terms of profound long-lasting postoperative analgesia.

We observed that only 50% of the participants demanded rescue analgesia in group B whereas 97% needed additional tramadol supplementation in group A. Corresponding to this, there was a statistically significant decrease in mean rescue analgesic consumption of tramadol in group B amounting to 63mg, whereas it was 96 mg in group A (P = 0.003). These findings substantiate the opioid sparing effect of ketamine when used as an adjunct to levobupivacaine and an abatement in opioid-related side effects such as nausea, vomiting, pruritus, and sedation. Demiraran et al. studied 90 patients undergoing cesarean section under general anesthesia, where the wound was infiltrated with 20 ml of 0.25% levobupivacaine at the end of surgery. They observed a total tramadol consumption of 483 mg in the study group and 560 mg in the placebo group (P = 0.07). The overall higher tramadol consumption in the study group than in group A can be attributed to the use of less concentration and lesser volume of levobupivacaine in their study. In addition, we used multimodal analgesia by giving intravenous injection of diclofenac 75mg 8 hourly to all the parturients which was not a part of their study.[8]

A Cochrane review encompassing 20 studies on parturients who received wound infiltration following cesarean section under regional anesthesia observed a statistically significant decrease in morphine consumption at 24 hours compared to placebo. However, this analysis revealed no additional advantage in terms of patient satisfaction score upon addition of ketamine to continuous wound infiltration with 0.125% bupivacaine, where the catheter was placed above the fascia affecting the spread of drug.[15] On the contrary, we observed a statistically and clinically significant improvement in the patient satisfaction scores of group B compared to group A (P = 0.02) which can be credited to the use of higher concentration, that is, 0.5% of levobupivacaine with ketamine.

There are various limitations of our study that are worth mentioning. First, the infiltration of local anesthetic was conducted by different surgeons, thus causing minor differences in the infiltration technique. Second, the duration of surgery that reflects the degree of tissue handling and inflammatory response which directly impacts on the degree of postoperative pain was not taken into account. Third, VAS score at movement was not recorded which could improve the analysis of pain and also the determine rate of early mobilization.

Our study was also superior to other studies in terms of inclusion of women in whom only pfannenstiel incision was given for cesarean section to avoid the type and nature of pain associated with surgical incisions. Superlatively, all drugs in local wound infiltration were used as per body weight in our study.

In conclusion, ketamine is an effective adjunct modality to levobupivacaine for local wound infiltration in terms of superior pain relief, lesser need for rescue opioid analgesia, and no major side effects.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Carvalho B, Cohen SE, Lipman SS, Fuller A, Mathusamy AD, Macario A, et al. Patient preferences for anesthesia outcomes associated with cesarean delivery. Anesth Analg 2005;101:1182-7.  Back to cited text no. 1
Ismail S. What is new in postoperative analgesia after cesarean sections? (Editorial) Anaesth Pain Intensive Care2012;16:123-6.  Back to cited text no. 2
Adeniji AO, AtandaOO. Randomized comparison of effectiveness of unimodal opioid analgesia with multimodal analgesia in post-cesarean section pain management. J Pain Res2013;6:419-24.  Back to cited text no. 3
Arias MG. Levobupivacaine. A long acting local anaesthetic, with less cardiac and neurotoxicity. Update in Anesthesia. http://e-safe-anaesthesia.org/e_library/03/Levobupivacaine_Update_2002.pdf. [Last accessed on 2019 Jul 12].  Back to cited text no. 4
Courtney KR, KendigJJ, Cohen EN. The rates of interaction of local anesthetics with sodium channels in nerve. J PharmacolExpTher 1978;207:594-604.  Back to cited text no. 5
Bajwa SJ, Kaur J. Clinical profile of levobupivacaine in regional anesthesia: A systematic review.J Anaesthesiol Clin Pharmacol2013;29:530-9.  Back to cited text no. 6
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Zeren S, Kesici S, Kesici U, Isbilir S, Turkmen UA, Ulusoy H, et al. Effects of levobupivacaine on wound healing. Anesth Analg2013;116:495-9.  Back to cited text no. 7
Demiraran Y, Albayrak M, Yorulmaz IS, Ozdemir I. Tramadol and levobupivacaine wound infiltration at cesarean delivery for postoperative analgesia.J Anesth2013;27:175-9.  Back to cited text no. 8
Bamigboye AA, HofmeyrGJ. Cesarean section wound infiltration with local anesthetic for postoperative pain relief – Any benefit? S Afr Med J 2010;100:313-9.  Back to cited text no. 9
Li X, Zhou M, Shi X, Yang H, Li Y, Li J, et al. Local anesthetic wound infiltration used for cesarean section pain relief: Ameta-analysis. Int J Clin Exp Med 2015;8:10213-24.  Back to cited text no. 10
Corsini T, Cuvillon P. Single doseintra incisional levobupivacaineinfiltration in cesarean postoperative analgesia: Aplacebo-controlled double-blind randomizedtrial. Ann Fr Anesth Reanim2013;32:25-30.  Back to cited text no. 11
McCartney CJ, 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.  Back to cited text no. 12
Adesope O, Ituk U, Habib AS. Local anestheticwoundinfiltrationfor postcesarean section analgesia: A systematic review and meta-analysis. Eur J Anaesthesiol2016;33:731-42.  Back to cited text no. 13
Abdallah NM, Salama AK, Ellithy AM. Effects ofpreincisionalanalgesia with surgical site infiltration ofketamineor levobupivacaine in patients undergoing abdominal hysterectomy under general anesthesia; A randomized double blind study. Saudi J Anaesth2017;11:267-72.  Back to cited text no. 14
Bamigboye AA, Hofmeyr GJ. Localanesthetic woundinfiltrationand abdominal nerves block during cesarean section for postoperative pain relief. Cochrane Database Syst Rev2009;3:CD006954.  Back to cited text no. 15


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4]


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