|Year : 2021 | Volume
| Issue : 1 | Page : 37-43
Efficacy of intravenous paracetamol infusion for prolongation of analgesia under spinal anesthesia for myomectomy
Jonathan C Eya, Fidelis A Onyekwulu, Adaobi O Amucheazi, Obinna V Ajuzieogu
Department of Anaesthesia, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria
|Date of Submission||06-May-2020|
|Date of Decision||25-May-2020|
|Date of Acceptance||14-Sep-2020|
|Date of Web Publication||21-Oct-2020|
Fidelis A Onyekwulu
Department of Anaesthesia, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu.
Source of Support: None, Conflict of Interest: None
Objective: To assess the effectiveness of intravenous (iv) paracetamol (PCM) infusion in prolonging the duration of analgesia following spinal anesthesia and to determine patients’ satisfaction with pain relief. Materials and Methods: This was a double-blind, randomized, controlled study. A total of 126 adult American Society of Anesthesiologists physical status I or II women scheduled for elective myomectomy under spinal anesthesia were enrolled in the study. Patients were randomly allocated into two groups. PCM group (group A) [n = 63] received 100mL of 1g PCM and Normal saline group (group B) [n = 63] received 100mL of normal saline after spinal anesthesia was established. Statistical analysis was done using Statistical Package for Social Sciences, version 17. Results: There was no statistical difference between the groups in terms of age, weight, and body mass index. The mean time to first analgesic demand was 4.75 ± 1.59 h in group A and 2.23 ± 0.15 h in group B (P < 0.001), while the mean dose of additional analgesic was significantly lower in group A (11.81 ± 2.50 µg) when compared to group B (255.49 ± 140.80 µg), P < 0.001. In group A, 75.8% expressed excellent satisfaction with pain relief while 62.9% of patient in group B reported poor satisfaction with pain relief (χ2 = 87.600, P < 0.001). Conclusion: Intravenous infusion of 1g PCM is effective in prolonging the duration of analgesia following spinal anesthesia for myomectomy.
Keywords: Intravenous paracetamol infusion, myomectomy, spinal anesthesia
|How to cite this article:|
Eya JC, Onyekwulu FA, Amucheazi AO, Ajuzieogu OV. Efficacy of intravenous paracetamol infusion for prolongation of analgesia under spinal anesthesia for myomectomy. Int J Med Health Dev 2021;26:37-43
|How to cite this URL:|
Eya JC, Onyekwulu FA, Amucheazi AO, Ajuzieogu OV. Efficacy of intravenous paracetamol infusion for prolongation of analgesia under spinal anesthesia for myomectomy. Int J Med Health Dev [serial online] 2021 [cited 2021 Jan 28];26:37-43. Available from: https://www.ijmhdev.com/text.asp?2021/26/1/37/298780
| Introduction|| |
Acute pain is an unpleasant perioperative experience. Approximately 80% of patients experience acute pain after surgery. Its management is increasingly characterized by multimodal or preventive approaches.
In 2004, the American Society of Anesthesiologists (ASA) Task Force published the first set of guidelines in dealing with perioperative pain management and strongly recommended the adoption of multimodal analgesia protocol for all surgical patients. The multimodal analgesic approach uses lower doses of different drugs with different mechanisms of action which acts synergistically to provide adequate analgesia and decrease side effects. This important concept employs the theory that agents with different mechanisms of action may have synergistic effects in preventing or treating acute pain when used in combination. This approach must be tailored to individual patients keeping in mind the procedure being performed, side effects of individual medications, and patients preexisting medications.
The purpose of the guidelines is to facilitate the safety and effectiveness of acute pain management in intraoperative setting. This is to reduce the risk of adverse outcomes, to maintain patients’ functional abilities as well as physical and psychological wellbeing, and to enhance the quality of life for patients with acute pain during the perioperative period. An adverse outcome that may result from insufficient treatment of pain is enormous. These include a delayed return of normal physiological functions, restriction of mobility with risk of thromboembolism and heightened catecholamine response leading to increased oxygen consumption, pulmonary dysfunction after surgery, additional time spent in the hospital, needless suffering, impairment of health-related quality of life, and development of chronic pain.
Spinal anesthesia is a safe and popular pain management technique used in gynecological surgeries. In spite of this, spinal anesthesia alone may not offer sufficient analgesia in major gynecological surgeries such as myomectomy. Although the use of epidural anesthesia may offer sufficient analgesia in major gynecological surgeries such as myomectomy, it has some drawbacks. Epidural anaesthesia is a difficult technique, requires specially trained anaesthetists to administer it, and its more expensive when compared to spinal anaesthesia. These may constitute limitations, especially in poor resource settings, that will hence have spinal as an option. Therefore, assessing the effectiveness of iv paracetamol (PCM) infusion as a multimodal approach to pain management following spinal anesthesia for myomectomy intraoperatively is paramount.
| Materials and Methods|| |
This was a double-blind, randomized study that was conducted in a tertiary hospital in Sub-Saharan Africa. Ethical approval for the study was obtained from the hospital’s ethics committee and written informed consent was obtained from the patients.
The sample size for the study was calculated based on the previous study by Dipasri et al. Using a significance level of 5% and power of study of 80%, 126 adult women who were American Society of Anaesthesiologists (ASA) class I or II and aged between 18 and 45 years scheduled for elective myomectomy were recruited into the study. This was from April 2014 to March 2015 (a period of 12 months). Patients with the uterine fibroid of 16 to 18 weeks gestation size estimation were recruited for the procedure. Patients with a history of local anesthetic allergy, PCM allergy, sepsis at the site of the procedure, coagulopathy, postmenopausal women, previous history of pelvic surgeries which may have adhesions and could elongate the duration of surgery, and patients who refused to participate were excluded from the study.
At preoperative visit, patients’ medical history was taken and clinical examination was carried out and body mass index (BMI) was calculated from patients' height and weight. Patients were allocated to one of the two groups: PCM group (group A) or normal saline groups (group B). The number of cards representing each of the two groups placed in a sealed brown envelops were put into a box and shuffled. The total numbers of sealed envelopes were equal to the sample size. Patients were allocated randomly to either of the two groups. This was carried out by a research assistant blinded to the study objectives, before patients were brought into the theater. In the theater, intravenous access was secured using a size 16 gauge cannula. The vital signs monitored were heart rate (HR), noninvasive blood pressure (NIBP), mean arterial pressure, electrocardiography (ECG) for cardiac activity, and arterial oxygen saturation (SpO2), using a DAS 4000 multiparameter monitor (GE, Medical Systems Information Technologies, Inc., Wisconsin, USA). The patient was preloaded with 0.9% normal saline 10mL/kg over 15 min. Using an aseptic technique, spinal anesthesia was administered with a 25 G pencil-point needle (Whitacre) and 15mg of 0.5% hyperbaric bupivacaine at L4/L5 or L3/L4 lumbar interspaces. The iliac crest was used as a land mark. The monitoring was done every 2 min while keeping verbal contact with the patient. The level of sensory block was determined sequentially with cold discrimination using cotton wool soaked in methylated spirit and loss of pain sensation by using a pin-prick test with a 23 G hypodermic needle. This was done bilaterally at the midclavicular line by a blind assessor in a cephalad to caudal direction.
Assessment of the degree of the motor block associated with an intrathecal block was evaluated using the Bromage score.
The Bromage score
When the block height reached up to T6, dermatome surgery was started. Intravenous PCM 100mL (1g) or placebo (100mL) was infused using a similar bottle by an assistant who was not involved in data collection. The patient and the researcher were not aware of which drug was administered. The study ended 6 h after administration of the test drug.
Hemodynamic variables were recorded at every 5 min intervals. A 20% decrease in systolic blood pressure compared to the baseline value was regarded as hypotension and was treated with iv ephedrine 6mg. Bradycardia was defined as HR lower than 60 beats per minute and was treated with iv atropine 0.6mg. Pain assessment was done using the numerical rating scale (NRS)., It is on the scale of 0–10, with 0 being no pain at all and 10 being the worst pain imaginable. Intravenous fentanyl 5 µg/kg was administered to women who developed pain with the NRS score >4 in the course of study.
Data were collected with forms designed for the study. Data were presented in tables and figures. Statistical analysis was done using Statistical Package for Social Sciences (SPSS, version 17). The statistical association was done using Student t-test for numerical variables and χ2 test for any categorical variables. The study ended 6 h after the administration of the content of the bottles used for the study.
| Results|| |
A total of 126 women for elective myomectomy were recruited for this study; 63 for each group. The spinal block could not be established in 2 patients and so were converted to general anesthesia and thus excluded from the study. The women were aged between 18 and 45 years with a mean of 36.63 ± 6.66 years for group A (n = 62) and 38.92 ± 4.44 years for group B (n = 62) [Table 1]. [Table 1] shows that, apart from the mean age in the PCM group which showed a significant difference when compared to the normal saline group, all other demographic data in the PCM group when compared to the normal saline group did not show any significant difference (P > 0.05). The P values are height (P = 0.255), weight (P = 0.940), and BMI (P = 0.450).
|Table 1: Demographic characteristics of group A compared with the group B|
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At 90 to 150 min after induction of spinal anesthesia, 37.1% of patients in the PCM group required additional analgesia as compared to 87.1% of patients in the normal saline group [Table 2]. Patients with the NRS score recording greater than 4 were given rescue analgesic (fentanyl 0.2 µg/kg intravenously). Moderate pain is at a pain score of 4–6. In group A, 62.9% had a mean pain score less than 4 while none among group B had mean pain score less than 4 six hours after iv PCM and normal saline administration [Table 2]. The difference in the pain score between the two groups was statistically significant (χ2 = 56.483, P < 0.001).
|Table 2: Proportion of patients requiring additional analgesia within 90 to 150 min of spinal anesthesia and pain score at 6 h|
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The mean time to first analgesic demand for the PCM group (4.75 ± 1.59 h) was significantly longer than that of the normal saline group (2.23 ± 0.15 h) (P < 0.001). The mean dose of additional analgesic for PCM group 11.81 ± 2.50 µg was significantly lower than that of the normal saline group 255.49 ± 140.80 µg (t = 13.683, P < 0.001). There was no statistically significant difference in the incidence of side effect and the total dose of ephedrine used in both groups [Table 3].
The onsets of sensory and motor blocks were not significantly different between the two groups, as well as the duration of motor block and duration of surgery [Table 4]. In the PCM group, 75.8% expressed excellent satisfaction with pain relief while 62.9% of the normal saline group reported poor satisfaction with pain relief [Table 5]. These proportions were significantly different (χ2 = 87.600, P < 0.001).
|Table 4: Comparison of sensory, motor block, and the duration of surgery between the two groups|
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The baseline vital signs and the values in the first 20 min after spinal anesthesia in both groups are similar as shown in [Figure 1] and [Figure 2].
|Figure 1: Baseline vital signs and the values in the first 20 min after spinal anesthesia in the PCM group. HR = heart rate; SBP = systolic blood pressure; DBP = diastolic blood pressure; MAP = mean arterial blood pressure; SpO2 = oxygen saturation; bpm = beats per minute.|
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|Figure 2: Baseline vital signs and the values in the first 20 min after spinal anesthesia in the normal saline group. HR = heart rate; SBP = systolic blood pressure; DBP = diastolic blood pressure; MAP = mean arterial blood pressure; SpO2 = oxygen saturation; bpm = beats per minute.|
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| Discussion|| |
This study demonstrated that iv PCM infusion administered after the establishment of spinal anesthesia prolonged the duration of analgesia, increased the time to first analgesic demand, reduced the pain scores, and provided greater satisfaction with pain relief among patients. These findings are comparable to those in the studies conducted in other parts of the world.,
Pain assessment is complex because it is influenced by emotional, cognitive, cultural, and ethnic factors. To standardize and make the assessment more objective, scales for pain assessment were created. Among the other methods, numerical rating scale (NRS) which was used in this study had better compliance, better responsiveness, ease of use, and good applicability when compared with visual analog scale (VAS) and verbal rating scale. Bijur et al. showed that NRS scores were strongly correlated to VAS scores at all time periods during a prospective cohort study of a convenience sample of adults presenting with acute pain to an urban emergency department and that the verbally administered NRS can be substituted for the VAS in acute pain measurement.
In this present study, few patients in the PCM group required additional analgesia when compared to the normal saline group. This shows that iv PCM prolonged the duration of action of analgesia under spinal anesthesia when compared with the placebo. This is in line with the findings in Dipasri et al. study. However, there were variations in the intervals of assessment of additional analgesia requirement. In this present study, the proportion of the groups requiring additional analgesia within 90 to 150 min of spinal anesthesia was demonstrated. This was not the case in Dipasri et al. study although their study similarly showed prolonged duration of analgesia by the PCM group. The duration of action of bupivacaine is 90 to 150 min.
The time to first analgesic demand was longer in group A when compared to group B. This indicates better analgesia provided by iv PCM infusion when compared to intravenous normal saline infusion under spinal anesthesia. In a study by Dipasri et al., their results also showed prolonged time to first analgesic demand in the PCM group when compared with the normal saline group. The differences in the time to first analgesic demand between our study (which was shorter in ours) and that of Dipasri et al. for both PCM group and saline group (8.1 ± 0.5 h vs 4.3 ± 0.4 h, respectively) could be due to ethnic differences and/or differences in the age of the patients used. They used patients aged 30 to 60 years as against 18 to 45 years used in this present study. Inclusion of older patients in relation to younger adults may affect the response pattern., This may be attributed to pain transmitting C and A delta peripheral nerve fiber function which declines progressively with age.
Choudhuri et al. had similar findings. Their result showed that the time to first analgesic demand was longer (8.144 ± 0.487 h in the PCM group and 4.27 ± 0.304 h in the normal saline group), than this present study. Variation in the time to first analgesic demand could be due to inclusion of elderly patients,, in their study as against younger adults in this index study. A study by Kaye et al. showed that treatment of pain may be complicated by multiple problems that are far less likely to occur in younger adults. Barriers to effective pain management include challenges to proper pain assessment, understanding of pain by patients, and atypical manifestations of pain in the elderly. Therefore, inclusion of elderly patients may also have been responsible for the variations in the lengths of time to first analgesic requests. Also, Choudhuri et al. used a higher volume of bupivacaine in spinal anesthesia which could have prolonged the duration of analgesia and time to first analgesic requirement when compared to this present study.
Although Choudhuri et al. used patients with ASA classes I and II similar to this present study, they recruited patients aged 35 to 70 years as against 18 to 45 years in this present study. They also administered 3.5mL of 0.5% hyperbaric bupivacaine in spinal anesthesia when compared to 3mL of 0.5% hyperbaric bupivacaine used in this present study. They used VAS in recording severity of pain as against NRS that was used in this index study.
Other studies have supported the effectiveness of iv PCM infusion. Sen et al. in their study showed that the iv PCM prolonged the duration of analgesia during iv regional anesthesia. Synergistic interaction between PCM and local anesthetics during iv regional anesthesia with lidocaine showed decreased tourniquet effect, increased anesthetic quality, and decreased postoperative analgesic consumption. Khalili et al. compared the efficacy of preemptive or preventive iv PCM with placebo in patients undergoing lower extremity orthopedic surgery under spinal anesthesia. Their study showed that both regimens of PCM provided superior analgesia 6 h after surgery than the placebo did and decrease postoperative analgesic consumption. A similar result was also reported by Sinatra et al. The underlying mechanism of this effect may be because PCM has always been thought to have a strong central action; supported by the fact that PCM is found in significant concentration in the cerebrospinal fluid after infusion in adults and children.
The key advantage of iv PCM seems to be that 1g of iv PCM is associated with about twice the plasma concentration effect as 1g of its oral or rectal application, resulting in greater central nervous system penetration which corroborates the superior analgesic efficacy seen with iv compared to oral PCM in the surgical setting. Because of its efficacy, a good margin of safety, and better patients satisfaction, iv PCM is an attractive component of a multimodal analgesic treatment plan.
Use of povidone–iodine as an antiseptic before central neuraxial injection instead of the 0.5% chlorhexidine gluconate as recommended by the members of the study guideline for skin antiseptic use. This is because povidone–iodine is what was available at the time of this study. Also cutting spinal needles were used during the conduct of spinal anesthesia. The incidence of post-dural puncture headache is high with cutting than with pencil-point needles in contemporary practice. But pencil-point needles were not readily available.
There were few articles that were directly related to the study. Specifically, studies that addressed the gynecologic surgical population. More work need to be done in this area and future research that duel on whether iv PCM reduces opioid-related adverse effects in a multimodal approach to postoperative pain management.
| Conclusion|| |
Intravenous infusion of 1g of PCM is effective in prolonging the duration of analgesia following spinal anesthesia and has minimal side effects. Several methods have been used to achieve the prolongation of pain under spinal anesthesia, but with various setbacks. The use of 1g iv PCM infusion is being advocated as cheap, easily accessible, and with relatively milder side effect that will prolong the duration analgesia under spinal anesthesia when compared to opioids that will cause respiratory depression, sedation, and itching and it is costly., We recommend the use of iv infusion of 1g PCM in the management of intraoperative pain following spinal anesthesia for myomectomy that can be done under spinal anesthesia.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Financial support and sponsorship
Conflicts of interest
The authors have no conflicts of interest relevant to this article.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]