The Spinal anesthesia (SA) is commonly used in cesarean sections (CS), and one of its most frequent side effects is post-dural puncture headache (PDPH) ( 1 ). PDPH is significantly more common in patients who had CS than other patients operated under SA, and its incidence is varied between 0.1-36%, according to the published studies. Nausea, vomiting, photophobia, vertigo, and other quality of life-impairing symptoms accompany PDPH ( 2 ). Recently, intrathecal morphine has been used to prevent unwanted PDPH, and contradictory results have been reported regarding the effects of morphine in PDPH prevention and treatment, which might have been related to the intrathecal dose of morphine ( 3 ). Opioids may be used as adjuvants to increase sensory block levels, reduce the incidence of hypotension, and provide postoperative analgesia in CS ( 4 ).

The study aimed to investigate the effects of different doses of morphine used for this purpose on PDPH development in pregnant women scheduled for CS.

American Society of Anesthesiologists (ASA) I-II patients, aged between 18-40 years, undergoing CS under SA in the University Medical Faculty, who accepted to participate were included in the study after the Ethics Committee’s approval and obtaining the patients’ verbal and written consent. Patients with a history of PDPH or migraine, those with more than 1000 ml of intraoperative blood loss, obese cases with Body Mass Index (BMI), and patients in whom regional anesthesia was contraindicated (sepsis, local infection, coagulopathy, cardiac disorder, hypovolemia) were excluded from the study. A total of 80 patients were included in this randomized, double-blind controlled study and divided into four groups of 20 patients as Group F25: 10mg of hyperbaric bupivacaine+25µg of fentanyl intrathecally, Group M100: 10mg of hyperbaric bupivacaine+100µg of morphine intrathecally, Group M150: 10mg of hyperbaric bupivacaine +150µg of morphine intrathecally, Group M200: 10mg of hyperbaric bupivacaine + 200µg of morphine intrathecally. All the patients were routinely monitored for Electrocardiography (ECG), Peripheral oxygen saturation (SpO ₂ ), heart rate (HR), and blood pressure after placing them on the operating table. Their systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), HR, and SpO ₂ values were recorded. The patients’ demographic data (age, gravida, parity, gestational age, BMI), operation times, the amounts of intraoperative blood loss, and intraoperative transfusions were recorded. SA was performed in a sitting position in all patients, using a 25 Gauche (G) sharp-tip spinal needle. A bilateral headache, with symptoms changing with the position, developing within the seven days following the dural puncture, and disappearing within 14 days was defined as PDPH. The occurrence of postoperative headaches, PDPH development, Epidural blood patch (EBP) requirement and its number, duration of hospitalization, and the maximal headache severity according to the visual analog scale(VAS) between 1-10 were recorded. The patients were monitored for side effects (nausea, vomiting, itching, desaturation), including drug allergies, within the first 24hours.

A total of 96 patients participated in the study. Since four patients participating in the study changed their minds on the operating table and underwent general anesthesia, they could not be included in the study. Since spinal anesthesia failed in seven patients, general anesthesia was performed, and they had to be excluded.

Because spinal anesthesia could not be achieved at the first puncture in three patients (was successful in the second or third attempt), those patients were also excluded. Finally, two patients were excluded from the study due to more than 1000 ml of intraoperative blood loss. The study was completed with 80 patients in total. The patients’ demographic data were presented in Table-1. The 5th-day VAS score was significantly higher in Groups F25 and M150 than Groups M100 and M200 (p<0.05). The PDPH treatment ratio in Group F25 was significantly higher than the ratio in Group M200 (p<0.05). All groups were similar regarding the ratio of pain other than PDPH (p>0.05) (Table 2). The highest VAS score in Group M200 was significantly lower than those of the F25 and Group M100 and M150 (p<0.05). The F25 and Group M150 and M150 did not differ significantly (p>0.05) regarding the highest VAS score (Figure 1).

On the fifth postoperative day, the PDPH VAS scores of Groups F25 and M150 were significantly higher than those of Groups M100 and M200 (p<0.05) (Figure-2). The comparison of the patients treated according to their groups was shown in Figure-3. There were no significant differences among the patient groups regarding their intraoperative and postoperative diastolic blood pressures, SpO ₂ value, and pulse rate (p>0.05). The 20-minute systolic blood pressure and blood pressure were significantly higher in Group F25 and M150 than M200 (Supplemental Table 1-5). Operative times, amounts of blood loss, hospitalization duration, and requirement rates for EBP of all groups were presented in Table- 3. The nausea-vomiting rate was lower in the F25 than M100, M150, and M200 (Table-3). The itching rate was lower in the F25 than M100, M150, and M200. Groups M100, M150, and M200 did not differ regarding the itching rate.

PDPH is the most common complications of SA widely used in CS ( 1 ). It is significantly more common in patients who had CS than in other patients operated under SA, and its incidence varies between 0.1 and 36% ( 2 ). Controversial study results have been reported regarding preventing unwanted PDPH by morphine administered intrathecally ( 3 ). Whitacre and Sprotte-type spinal needles have a lower risk of PDPH ( 6 ). Most frequently, it has been reported in patients in whom a 20-22G standard Quincke needle was used for diagnostic lumbar puncture ( 7 ). The incidence of PDPH was reported as 8.7 in patients in whom a 25G Quincke needle was used. This study investigated the effects of intrathecal administration of different doses of morphine and fentanyl on post-dural puncture headache development after CS under spinal anesthesia, and PDPH occurred in 31% of pregnant women. However, many reasons affect the development of PDPH regardless of the needle type.

Methods such as rehydration, analgesia, resting, and EBP have been used for treating PDPH ( 8 ). In the present study, oral fluids were administered in dehydrated patients to treat PDPH. Additionally, infusion of 200 mg of theophylline intravenously and a combination of paracetamol 250 mg/propyphenazone 150 mg/caffeine 50 mg was orally administered when required. PDPH regressed with treatment, and none of the patients required an EBP. PDPH was most common in the fentanyl group, whereas its last occurrence was in M200. The other groups did not differ significantly regarding the incidence of PDPH. The highest VAS score of Group M200 was significantly lower than those of Groups F25, M100, and M150 (p<0.05). Groups F25, M100, and M150 did not differ regarding the highest VAS score (p>0.05). No significant differences were determined between the postoperative first four days and the postoperative sixth and seventh days regarding the VAS scores. Abboud et al. ( 9 ) investigated the effect of morphine on PDPH in their study involving 82 cesarean cases in ASA I and II risk groups. They divided the cases into two groups, and in addition to the local anesthetic, they administered 0.2 mg of morphine intrathecally in 40 patients in the first group and 0.2 ml of saline in 42 patients in the second group. They monitored their patients for three days regarding PDPH. Similar to our study results, they did not determine significant difference for PDPH between the groups within the first postoperative three days. When we analyzed nausea-vomiting, desaturation, itching, apnea, and as the cases’ side effect profiles, no difference was present for desaturation and apnea rates.

Sawi et al. ( 10 ), in their study involving 60 ASA I-II cesarean cases, compared intrathecal administration of morphine + bupivacaine + fentanyl with intrathecal bupivacaine + fentanyl. They determined that postoperative nausea-vomiting and itching incidences were higher in the group that received intrathecal morphine than the group that received intrathecal fentanyl only. Pınar et al. reported ahigher incidences of postoperative nausea-vomiting and itching in the morphine ( 11 ). Similarly, we determined in our study that Group F25 had significantly lower nausea-vomiting and itching rates than Groups M100, M150, and M200. No significant differences were present among Groups M100, M150, and M200 regarding the nausea-vomiting and itching rates. Pınar et al., in their study involving 60 cesarean cases in ASA I and II risk groups, compared intrathecal levobupivacaine + fentanyl with intrathecal levo bupivacaine + morphine ( 11 ). They could not find any significant difference among the intraoperative hemodynamic parameters in the morphine group. Similar to the literature, we could not determine any significant difference among the groups regarding the evaluated hemodynamic data (pulse, SAP, DAP, MAP, and SpO ₂ ). However, the 20th minute SAP value was significantly higher in groups F25 and M150 than Group M200. Besides, the 20th minute MAP values of Groups F25, M100, and M150 were significantly higher than Group M200. However, there are plenty of factors affecting parameters, such as the fetus’s emergence time, the amount of bleeding, and vasodilator effect of oxytocin when applied differently from each other. Postpartum eclampsia and subdural hematoma, angiopathy, meningitis, cerebral vein thrombosis and sinuses, stroke, pituitary tumor,and choriocarcinoma may be mentioned in the etiology of secondary headache in the postpartum period ( 12 ). In our study, no significant differences were present among the groups regarding headaches other than PDPH. The limitation of this study is its small sample size.

The incidence of PDPH was lower in the group that 200 µg of morphine was administered intrathecally. In the morphine receiving groups, the incidence of side effects (nausea-vomiting, itching) was dose-independently higher than the fentanyl administered group. Because of its small sample size, our studies should be supported by more extensive studies to reach definitive conclusions.