Spinal anesthesia is a commonly used technique for lower abdominal, pelvic, and lower limb surgeries due to its simplicity, rapid onset, and effective intraoperative anesthesia. Local anesthetic such as hyperbaric bupivacaine is a long-acting amide anesthetic. It has been commonly used for spinal anesthesia due to its favorable sensory and motor blockade characteristics. However, one of the disadvantages is the postoperative duration of analgesia is limited often necessitating the use of adjuvants to manage postoperative pain this may lead to increased use of analgesics which can compromise safety and increase the risk of side effects [1]. Opioids such as morphine when administered intrathecally act on the opioid receptors in the dorsal horn of the spinal cord. It increases the quality and duration of analgesia. Morphine is water soluble allowing it to remain in the CSF for a longer duration and providing prolonged postoperative analgesia [2]. However, its use is associated with important side effects such as nausea, vomiting, pruritus, urinary retention, and in rate cases dose-dependent respiratory depression [3].  Therefore, determining the optimal intrathecal dose of morphine that provides sufficient analgesia and minimizing adverse effects is important. Studies done in this field previously have demonstrated that the efficacy of adding morphine doses ranging from 50 µg to 300 µg to spinal anesthesia provided adequate analgesia. A dose of 100µg is considered effective for many patients. At this dose, there appears a balance between the duration of anesthesia and the side effects [4]. Few studies have shown that doses of 200 µg have been linked to increased incidence of side effects without substantial analgesic effects [5]. Conversely, at lower doses, it may not provide adequate postoperative analgesia after major surgeries. Therefore, the ideal intrathecal morphine dose is a subject of research. Variability in patient characteristics, surgical procedures, and individual responses to opioids warrants more research to define safe and effective doses. Based on this background we in the current study aimed to compare three different doses of intrathecal morphine 100 µg, 200 µg, and 300 µg added to hyperbaric bupivacaine and assess the block characteristics, duration of analgesia, hemodynamic stability, and incidence of side effects.

This study was done in a prospective double-blinded randomized manner.  The study was conducted at the Mahatma Gandhi Memorial Hospital, Warangal, and Government Maternity Hospital, Hanumakonda 2021-2024 on 90 patients of ASA I and II undergoing infraumbilical surgeries. This study was done after ethical committee approval and written informed consent was obtained from all patients included in the study.

Inclusion criteria

1. Patients in the age group of 20 to 50 years
2. ASA I and II Infraumbilical surgeries
3. Males and Females
4. Willing to participate in the study

Exclusion criteria

1. Age <20 yrs and > 50 yrs ASA III and IV
2. Contraindication to spinal anesthesia
3. Patients with decreased cardiorespiratory reserve-COPD, Bronchial asthma
4. H/o allergy to morphine

 Study Population

90 patients were included in this double-blinded randomized controlled study. Patients were divided into 3 groups of thirty patients each. Patients in group M1 received 3ml of 0.5% hyperbaric bupivacaine plus 50µg preservative-free morphine 0.2ml. Patients in group M2 received 3ml of 0.5% hyperbaric bupivacaine plus 100µg preservative-free morphine 0.2ml. Patients in group M3 received 3ml of 0.5% hyperbaric bupivacaine plus 200µg preservative-free morphine 0.2ml.

Patients who satisfy the inclusion criteria are selected and they undergo thorough preoperative evaluation which includes the following history of underlying medical illness, previous surgery, anesthesia, and hospitalization. Physical examination, general condition of the patient vital signs height and weight examination of CVS, RS, CNS Airway, and Spine examination

Hb%, HCT, BT/ CT, Platelet count, RFT, Blood sugar, ECG, CXR, Blood grouping, and cross-matching were done. Patients who satisfied the inclusion criteria were explained about the nature of the study and the anaesthetic procedure. Written Informed consent was obtained from all the patients taken up for study. Randomization of the cases as per the group and the drug preparations were made by the anaesthesiology consultant who did not participate in the study. I performed the subarachnoid block and made intraoperative and postoperative observations.

Preparation

In the Operating room, appropriate equipment for airway management and emergency drugs were kept ready. Then the patients are shifted to the operation theatre. With strict aseptic precautions, the intravenous line started with an 18G i.e. cannula and crystalloids. Pulse Oximeter, E.C.G. Monitor, and Non-invasive blood Pressure cuff connected to the patient.

Patient turned to right lateral position, under aseptic precautions midline lumbar puncture was performed using 25G Spinal needle in L2-L3/L3-L4 space and after free flow of CSF, drug solution appropriate for the groups given. The patient turned immediately to supine position. Time of injection of drug into the intrathecal space was considered as 0 min.

Block Level Sensory Level

Assessed by loss of sensation to pinprick using 23 G needle every 15 secs till loss of sensation to pinprick at L2 level. The onset of sensory block was taken as time from intrathecal injection to loss of pinprick sensation at L2. After 20 mins of performing spinal block, the dermatome level of sensory block was noted and was considered as maximum sensory block.

Motor Blockade by Modified Bromage Scale

Full movement of legs and feet. Just able to flex the knees with free movement of feet. Unable to flex knees but with free movement of feet. Unable to move legs and feet. All patients received supplemental oxygen by Hudson mask at 5lts/min. Intraoperative fluids are given by appropriate fluid requirements for individual patients.

Intraoperative monitoring of vital signs and side effects intraoperative hypotension was treated with crystalloids and Inj. Ephedrine 3 mg when required. The patient's pulse rate, NIBP, respiratory rate, SPO2, ECG, and pain score were monitored throughout the procedure. Intraoperative and postoperatively patients were assessed for sedation, analgesia, and side effects using appropriate scores.

Assessment of sedation and pain

Sedation was assessed using a 4-point sedation score0-awake and alert in the PACU, pain assessment using VAS was done using the VAS scale till a VAS score >2 was reached. If the patient complains of pain, rescue analgesic Inj. Diclofenac 75mg i.m. was given. Duration of effective analgesia was defined as the time interval between the onset of SAB and the time to reach VAS >2. Vital signs and occurrence of side effects - sedation, nausea & vomiting, pruritis, urinary retention, and respiratory depression were monitored postoperatively for 24 hrs.

Statistical analysis

 All the available data was refined, segregated, and uploaded to an MS Excel spreadsheet and analyzed by SPSS version 22 in Windows format. The continuous variables were represented as mean, standard deviation, and percentages, and the categorical variables were calculated by Pearson's chi-square test. The values of p (<0.05) were considered as significant.

The mean age distribution was 36yrs in group M1, 37yrs in M2, 34yrs in M3. There was no statistically significant difference among the age groups and hence the groups are comparable concerning age. The mean height of the patients was 162 cm in group M1, 163 cm in group M2, and 162 cm in group M3, with no statistical difference among them. Therefore, the groups were comparable in terms of height. The mean weight distribution was 57 kg in M1, 57 kg in M2, and 59 kg in M3, and there was no difference between them; thus, the groups were comparable concerning their weight (Table 1). 

The most common procedures in this study were other procedures including Hydrocele surgery, Varicocelectomy, Hemorrhoidectomy, and Fistula-in-ano or Fissure surgery ranging from 60% to 70% in the three groups given in Table 2. The other procedures included abdominal hysterectomy in 25 – 30% of cases other procedures are represented in table 2.

The mean time for the onset of sensory block was 122secs for M1,123secs for M2, and 118s for M3, and the groups did not differ significantly concerning the onset of sensory block. The mean time for the onset of motor block was 106 s for M1, 102 s for M2, and 103 secs for M3, and the groups did not differ statistically concerning the onset of motor blockade. The time for the two-segment regression was 128 min for group M1, 126 min for M2, and 127 min for M3, and the groups did not differ statistically concerning the two-segment regression of sensory block. The duration of the motor block was 187 min in Group M1,191 mins in M2 and 191 min in M3, and the groups did not differ statistically concerning the duration of motor blockade. The mean intraoperative heart rate was 76 beats/min in group M1, 74/min in M2, and 71 beats/min in group M3, and there was a statistically significant difference between the groups. The mean postoperative heart rate was 78 beats/min in group M1, 72/min in M2, and 71 beats/min in M3, and there was a statistically significant difference between the groups. Thus, there was a significant difference between the groups concerning the intraoperative and postoperative heart rates.  The intraoperative mean arterial blood pressure was approximately 84 mmHg in all three groups and was statistically insignificant. The postoperative mean arterial blood pressure was 82 mmHg in group M1, 81 mmHg in group M2, and 82 mmHg in group M3, and they were statistically insignificant (Table 3).

Thus, the three groups did not differ statistically concerning the mean arterial blood pressure. The mean duration of analgesia was 7 h in group M1, 18 h in group M2, and 24 h in group M3, which was statistically significant. Thus, there was a statistically significant difference in the duration of analgesia between the groups, showing that group M3 had the longest duration of analgesia (Table 4).

There was no incidence of nausea and vomiting in Group M1, but eight patients in Group M2 and seven patients in Group M3 had incidences of nausea and vomiting. Thus, the three groups did not differ in the incidence of nausea and vomiting. There was no occurrence of pruritus in groups M1 and M2, and 5 patients in group M3 had pruritus. Thus, there was a statistically significant difference between the three groups showing that group M3 had the incidence of pruritus among the three groups. The incidence of urinary retention was 4 patients in group M1, 7, and 8 patients in groups M2, and M3, respectively; however, the difference was not statistically significant. There was no significant difference in the incidence of urinary retention between the three groups. The mean intraoperative respiratory rates were 15 min in M1, 15/min in M2, and 16/min in M3. There was a statistically significant difference, but it was not clinically significant. The mean intraoperative saturation was approximately 99% in all groups, with no statistical difference between them. The mean postoperative saturation was approximately 98% in all three groups. There was a statistically significant difference between them, but the difference was not clinically significant.

Effective and prolonged analgesia is critical for enhanced recovery following surgeries. Most of the time intravenous analgesics such as narcotics and NSAIDs often provide short-lasting relief. However, in some cases repeated doses may be required which enhances the risk of adverse effects. This limitation can be solved by intrathecal administration of opioids which prolonges analgesia and has better efficacy and tolerability. Wang et al. were the first to describe intrathecal morphine use in 1979 [2]. Following this discovery it has been now used across various surgical procedures. Morphine is a hydrophilic opioid when added to hyperbaric bupivacaine in spinal anesthesia has been shown to produce excellent surgical analgesia which can last up to 30 hours. This facilitates early ambulation and reduces the risk of analgesia requirements postoperatively [6, 7] in the present study we found that patient demographics in all three 3 groups were equally distributed (Table 1) and no significant differences were observed based on age, height, and weight. The onset of sensory and motor blocks or the time to two-segment regression was also comparable in the three groups and no significant differences were observed similar findings have been reported by other studies in this field. [6, 8] Demiraran et al. [9] also observed that the duration of motor block was similar in all three groups.

The hemodynamic profile shows the trend towards lower intraoperative and postoperative heart rates in the morphine group as compared to other groups which could be due to better analgesia and reduced stress response. These findings were consistent with the study of Karaman et al. [10] who reported a similar trend in the morphine group. The mean arterial pressure remained stable across all groups in concordance with the findings of Kong et al. [11] who showed improved analgesia without significant hemodynamic disturbances.

The important noteworthy differences between the groups were about the duration of postoperative analgesia which was 7 hours in the M1 group and 18 hours in the M2 and M3 groups. This increase in analgesia duration with higher doses has been reported by previous studies by Abouleish et al. [12], Gehling et al. [13], and Demiraran et al. [9]. The adverse effects commonly associated with intrathecal morphine included nausea, vomiting, pruritus, urinary retention, and respiratory depression. This study found that incidences of nausea and vomiting were higher in M2 and M3 groups consistent with observation of Gehling et al. [3] and Girgin et al. [14]. Interestingly, the incidence did not increase between 100 µg and 200 µg groups, suggesting a threshold effect. Pruritus was commonly associated with the M3 group however, it was self-limiting, and similar dose-related adverse reactions have been shown by Abboud et al. [8], Gehling et al. [13], Nakamura et al. [15], and Girgin et al. [11]. In this study, none of the patients developed significant respiratory depression and all maintained acceptable respiratory rates and oxygen saturation. This was in agreement with the findings of Gehling et al. [13], and Sultan et al. [16], indicating that doses below 300 µg are generally safe in terms of respiratory compromise. Since morphine is hydrophilic in nature and allows slow rostral migration in CSF prolonging the spinal analgesia effects by action on dorsal horn neurons. Some adverse effects could be because of cephalad spread to the medullary chemoreceptor trigger zone and serotonergic pathway stimulation [17].

This study found that intrathecal morphine in doses up to 200 µg provides effective and prolonged postoperative analgesia with minimal and manageable side effects. Its incorporation into spinal anesthesia enhances patient comfort and reduces systemic opioid requirements.

1. Kehlet H. Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth. 1997;78(5):606–617.
2. Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology. 1979;50(2):149–151.
3. Gehling M, Tryba M. Risks and side-effects of intrathecal morphine combined with spinal anesthesia: a meta-analysis. Anesthesia. 2009;64(6):643–651.
4. Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship of intrathecal morphine for postoperative analgesia in cesarean delivery. Anesthesiology. 1999;90(2):437–444.
5. Rathmell JP, Lair TR, Nauman B. The role of intrathecal drugs in the treatment of acute pain. Anesth Analg. 2005;101(5 Suppl):S30–S43.
6. Kong SK, Cheong DM, Wong YF, et al. Comparison of spinal morphine with epidural patient-controlled analgesia for post-cesarean delivery pain management. Acta Anaesthesiol Sin. 2002 Dec;40(4):169-74.
7. Kong SK, Cheong DM, Wong YF, et al. Comparison of spinal morphine with epidural patient-controlled analgesia for post-cesarean delivery pain management. Acta Anaesthesiol Sin. 2002 Dec;40(4):169-74.
8. Abboud TK, Dror A, Mosaad P, et al. Mini-dose intrathecal morphine for the relief of post-cesarean section pain: safety, efficacy, and ventilatory responses to carbon dioxide. Anesth Analg. 1988 Jul;67(7):137-43.
9. Demiraran Y, Korkut E, Tamer A, Yorulmaz I. The efficacy of intrathecal morphine for postoperative analgesia in patients undergoing total knee arthroplasty. J Opioid Manag. 2007 Jan-Feb;3(1):23-6.
10. Karaman S, Kocabas S, Dogru K, et al. Single dose spinal morphine for postoperative pain relief after cesarean section: a prospective randomized study. Clin Exp Obstet Gynecol. 2011;38(2):131-5.
11. Kong SK, Cheong DM, Wong YF, et al. Comparison of spinal morphine with epidural patient-controlled analgesia for post-cesarean delivery pain management. Acta Anaesthesiol Sin. 2002 Dec;40(4):169-74.
12. Abouleish E, Rawal N, Fallon K, Hernandez D. Combined intrathecal morphine and bupivacaine for cesarean section. Anesth Analg. 1988 May;67(5):370-4.
13. Gehling M, Luesebrink T, Kulka PJ. Intrathecal morphine for postoperative pain management--a review of the literature. Anesth Analg. 2009 May;108(5):1515-22.
14. Girgin NK, Gurbet A, Turker G, Aksu H, Kilic N. The effects of spinal morphine on postoperative analgesia and side effects in patients undergoing cesarean delivery. Acta Anaesthesiol Scand. 2008 Sep;52(8):1092-7.
15. Nakamura T, Kadoi Y, Saito S. The incidence of side effects with intrathecal morphine: influence of dose and time. J Anesth. 2013 Dec;27(6):857-60.
16. Sultan P, Gutierrez MC, Carvalho B. Neuraxial morphine and respiratory depression: finding the right balance. Drugs. 2011 Jun 18;71(9):1107-19.
17. Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology. 1979 Jul;50(1):149-51.