Morphine Patches

Overview:

The unrivaled post-surgical analgesia that spinal (intrathecal) morphine provides is undeniable. In thoracoabdominal and lower limb surgery, 100-200 mcg of morphine therapeutic dose is sufficient to provide strong pain (VAS 1-3). Respiratory depression is an uncommon and solitary occurrence. Here are some reactions to it.

Resp. 1. Dr. Vicente Barraza. November 24, 2005. Mexico. 

The dosage of intrathecal morphine that I use is 100 mcg, sufficient to avoid postoperative nausea and vomiting due to spinal opioids and infrequent itching. I suggest lowering the dose in the elderly (80 mcg). In obstetric patients, it is not expected to find significant concentrations of morphine in blood or milk. Diazepam IV can have undesirable effects. A colleague uses midazolam through the subarachnoid route, but the undesirable effects seem to make it of little use. I think the same about neostigmine, but what is worth it is clonidine which Dr. L Higgins has a great experience with. Also, in that case, I believe that the dose can be reduced appreciably without diminishing the benefits.

Resp. 2. Dr. Ernesto Maldonado Carreño. May 15, 2009. Celaya, Guanajuato, Mexico.

 There is underuse of morphine drugs in our environment due to ignorance, fear, and, in some cases, difficulty in obtaining them. In all the places where I work, I have morphine and fentanyl, and I do not hesitate to use them in daily procedures, not to mention in the pain clinic. The surgeon must be educated regarding the invaluable usefulness of opioids since they attribute to anesthesia any situation that in their opinion is attributable. This is why the great importance of the post-anesthetic visit where we must subtly emphasize to the patient and his family that we use morphine drugs; in this way, we educate society to "de-anesthetize" opioids.

Resp. 3. Dr. Luis Higgins. February 23, 2018. 

The two obstetricians I work with perform cesarean sections between 20 and 30 minutes, very complicated 45 minutes -exceptional-no more. The doses of hyperbaric bupivacaine 0.5% that I use are from 5 to 7.5 mg. The research recommends 12.5 mg because of more significant arterial hypotension and bradycardia. Which can be treated ideally with hypotension (ephedrine, phenylephrine) atropine0.5 mg Bupivacaine 10 mg only if the surgery would take more than 2 hours. I always combine bupivacaine with fentanyl 25 mcg and morphine 100-200 mcg. Spinal block with Quincke 26 or Whitacre 25-27 G needle. Preferably Whitacre. Surgical analgesia and muscle relaxation are unbeatable, reaching T3-T4 dermatomes. The postoperative analgesia that spinal morphine assures me is from 18 to 24 hours with a pain VAS of 0-2/10 in static pain and 1-3 emotional pain. Mild-moderate itching of the skin, arms, and face in 10% of our patients did not last more than 4-6 hours. NAVPO 10%, moderate-intense. I always administer, after blocking, dexamethasone 8 mg and ondansetron 8 mg IV. Postoperative ventilatory depression? It is possible but clinically irrelevant. I have never seen one in 15-20 years with this technique. Apnea? Never! doPost puncture headache? With Quincke 27, 1-2%, mild-moderate, no more than 3 days; with Whitacre, 0%. Headaches (Quincke), if they occur, are of mild-moderate intensity and are treated by the same obstetrician-gynecologist. With spinal blockade with this type of needle, I have not needed to place an epidural blood patch. 

Summary: spinal morphine is wonderful!

Resp. 4. Dr. Víctor Whizar Lugo. May 18, 2018. Tijuana, BCN. 

Fentanyl and spinal morphine are very safe and pharmacologically justified techniques. The former is closely related to lipids favors a less extensive fixation in the CNS while providing analgesia in a smaller number of spinal cord segments than morphine since the latter is more water-soluble and migrates cephalad. Adequate doses are a far cry from the respiratory depression that is generally mentioned. Of course, we must bear in mind the dose and the patient and the environment where the surgery and subsequent recovery are performed. In our practice, we use it as a routine and occasionally add clonidine, which allows us to improve anesthesia conditions and reduce the dose of local anesthetics.

Resp. 5. Dr. Luis Higgins. February 9. 2019. Mexico City. 

Intrathecal morphine, topic cited again and again in AMI-List. Intrathecal morphine is excellent postoperative analgesia, second to none. Below I present my casuistry of 100 cases for post-cesarean analgesia. Post-dural puncture headache : 0 with Whitacre; 3% with Quincke (mild, moderate, no more than 24 hours)

Resp. 6. Dr. Daniel Elinger. February 10, 2019. Buenos Aires, Argentina. I routinely apply ondansetron 8 mg and dexamethasone 8 mg, so nausea and vomiting are infrequent. In addition, we routinely administer ketorolac in the immediate postoperative period (we have not seen any tendency to more significant bleeding published in some articles). I recommend propofol 20 mg IV to treat the itching. Do not administer less than 5 mg intrathecal bupivacaine. Start with 7.5 mg and titrate as more subarachnoid blocks are applied. I do not apply more than 100 mcg of spinal morphine.

Here are some bibliographical references of interest:

1. The addition of morphine prolongs fentanyl-bupivacaine spinal analgesia to relieve labor pain. HM Yeh. Anesth Analg. 2001 Mar;92(3):665-8. 

Intrathecal fentanyl (25 mcg) and bupivacaine (2.5 mg) give appropriate labor analgesia for about 90 minutes. This prospective, random, double-blind study aimed to see if adding 150 mcg of morphine to a fentanyl (25 mcg) and bupivacaine (2.5 mg) intrathecal combination would prolong pregnancy analgesia. 95 healthy risk pregnancy women in childbirth received 2 mL of one of two intrathecal study solutions: FB (n=48): fentanyl (25 mcg) and bupivacaine (2.5 mg); o FBM (n=47): fentanyl (25 mcg), bupivacaine (2.5 mg) and morphine (150 mcg). The mean duration of labor analgesia was significantly longer in the FBM group than in the FB group (252 +/- 63 min versus 148 +/- 44 min, P<0.01). There were no significant differences between the two groups concerning sensory levels, the incidence of nausea, vomiting, pruritus, low blood pressure, or cesarean section. Adding 150 mcg of morphine to fentanyl and bupivacaine increased childbirth pain duration without increasing adverse effects.

2. Dr. uses low-dose intrathecal morphine and spinal bupivacaine in painkiller during c - the section. Nermin K Girgin. J Clin Anaesth. 2008 May;20(3):180-5.

• Objective: Low dosages of bupivacaine were used to enhance the amount of pain
• Intrathecal morphine was given in a 0 to 400 mcg dose for c-section analgesia.
• Design: Randomized, double-blind. University Hospital. One hundred full-term pregnant women, physical status ASA I and II, under cesarean section with subarachnoid block.
• Interventions: Patients were randomly assigned to one of 5 groups to receive 0, 100, 200, 300, and 400 mcg intrathecal morphine in addition to hyperbaric bupivacaine (7.5 mg). After surgery, each patient received patient-controlled intravenous (IV) analgesia (PCA) with morphine.
• Measurements: 24-hour intravenous PCA morphine use and visual analog scores for pain were recorded. 
• Nausea, 
• vomiting, 
• Pruritus scores were assessed intraoperatively and at 4-hour intervals for the first 24 hours postoperatively.
• Main results: PCA morphine was higher in the control group (morphine 0 mcg) than in the groups that received morphine 100, 200, 300, and 400 mcg intrathecally. There was no difference in intravenous morphine administration between the 100 and 400 mcg groups, despite a 4-fold increase in intrathecal morphine dose. There were no differences between the groups in nausea and vomiting, but pruritus increased directly to the dose of intrathecal morphine.
• Conclusions: The intrathecal dose of morphine 100 mcg produces comparable analgesia with doses as high as 400 mcg,
•  With significantly less itching when combined with low doses of bupivacaine.

3. Comparative study of fentanyl and morphine in addition to hyperbaric or isobaric bupivacaine in combined spinal anesthesia for cesarean section. Arch Med Sci. 2011 Aug;7(4):694-9.

• Introduction: To compare the effects of isobaric and hyperbaric bupivacaine combined with morphine or fentanyl in cesarean section. Quality, surgical anesthesia, analgesia, the need for postoperative analgesics, and side effects were evaluated.
• Material and methods:100 patients' physical status ASA I-II, 18 to 40 years old, randomized into 4 groups. Intrathecal solutions were isobaric bupivacaine + morphine (group A), isobaric bupivacaine + fentanyl (group B), heavy bupivacaine + morphine (group C), and heavy bupivacaine + fentanyl (group D). Mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SatO2), ephedrine consumption, analgesic requirement time, and additional analgesic requirements were recorded.
• Results: MAP was the lowest in all groups. HR significantly decreased in group A in the first 10 min, but not in the other groups. The decrease in visual analog scale (VAS) pain scores began in the groups after the 4th postoperative hour (p<0.05) and the VAS of group B, 8 hours later, was significantly greater than in the other groups. Postoperative analgesic requirement time was longer in patients who received intrathecal morphine compared to fentanyl. The duration of analgesia with isobaric bupivacaine and morphine was the longest.
• Conclusions: Intrathecal morphine provides longer postoperative analgesia, but this duration is prolonged when plain bupivacaine is combined instead of heavy bupivacaine.

4. Planned cesarean delivery and urinary retention associated with spinal morphine. Susan M DiBlasi. J Perianesth Nurs. 2013 Jun;28(3):128-36. 

Cesarean section is the second most common surgery in the United States. Preventing complications in this surgery is a priority in nursing care. Nurses at the study institution noted that post-cesarean section patients experienced an increase in urinary retention after the use of spinal morphine for postoperative pain relief. This observation prompted a review of the literature indicating that limited research has been conducted in this area. The purpose of this study was to explore the relationship of urinary retention at cesarean section and spinal morphine dose. A retrospective, the quasi-experimental, three-group design was used. Records of 150 patients, ages 17 to 39, undergoing elective cesarean section were reviewed. Morphine doses included 100, 150, and 200 mcg. No statistically significant differences were found between the three groups.

5. The Effect of Intrathecal Morphine Dose on Outcomes After Elective Cesarean Delivery: A Meta-Analysis. Pervez Sultan. Anesth Analg. 2016 Jul;123(1):154-64 .

• – Background: The dose of intrathecal morphine that achieves optimal analgesia for post-cesarean section analgesia while minimizing side effects has not been confirmed. In this meta-analysis, we aimed to determine whether low-dose or high-dose intrathecal morphine provides an acceptable duration and intensity of analgesia with fewer side effects.
• – Methods: Literature search (PubMed, EMBASE, MEDLINE, Scopus, Web of Science and CINAHL) to identify randomized controlled studies including patients undergoing elective caesarean section under spinal analgesia comparing low dose (DB 50-100 mcg) morphine with high dose (DA > 100-250mcg). The primary outcome was the time of the first request for supplemental analgesia. Secondary outcomes included pain scores, morphine use, maternal side effects (vomiting and itching), and Apgar scores. Mean differences (MD) and  odds ratios  (OR) were calculated using random-effects models with 95% confidence intervals (CI).
• - Results: Eleven articles met our inclusion criteria. 480 patients in all study groups (DA 233 patients, DB 247 patients). The mean time to first analgesic request was longer (MD, 4.49 h [95% CI, 1.85-7.13]; P=0.0008) in the AD  versus  DB group. Pain (scale 0-100) at 12 hours (MD, 2.54 [95% CI, -2.55 to 7.63]; P=0.33) as well as morphine consumption at 24 hours (MD, 1.31 mg [95% CI, -3.06 to 7.31]; P=0.42) were not significantly different. The incidence of nausea or vomiting (OR, 0.44 [95% CI, 0.27-0.73]; P=0.002) and pruritus (OR, 0.34 [95% CI, 0.20-0.59]; P=0.0001) was lower in the DB. The incidence of Apgar scores <7 at minute was not different between groups (OR, 1.11 [95% CI, 0.06-20.49]; P=0.94).
• – Conclusions: This meta-analysis shows that intrathecal morphine DA prolongs post-cesarean analgesia compared with DB. The MD of 4.5 hours (95% CI, 1.9-7.1 and 99% CI, 1-8.2 hours) of pain relief must be balanced against the increased risk of maternal pruritus and vomiting. Physicians can use the results of this study to weigh the benefits and potential side effects of using intrathecal morphine DA for post-cesarean section analgesia.

6. Perioperative analgesia after intrathecal fentanyl and morphine or morphine alone for cesarean section: A randomized controlled study. Wojciech Weigl. Medicine (Baltimore). 2017Dec;96(48):e8892 .

• – Objectives: Intrathecal morphine is used for post-cesarean section analgesia, but it may not be optimal for intraoperative analgesia. Intrathecal fentanyl could complement intraoperative analgesia when added to a local anesthetic and morphine without affecting postoperative pain management.
• – Methods: Prospective, randomized, double-blind, parallel group study included 60 pregnant women scheduled for elective cesarean section. Spinal analgesia consisted of bupivacaine with morphine 100 mcg (group M) or fentanyl 25 mcg and morphine 100 mcg (group FM). The frequency of intraoperative pain and meperidine consumption in the 24 postoperative hours were recorded.
• - Results: Fewer patients in the FM group required additional intraoperative analgesia (p<0.01, relative risk 0.06, 95% CI 0.004-1.04). The FM group was noninferior to the M group for 24-hour opioid use (95% CI: -10 mg to 45.7 mg, which was below the prespecified cutoff of 50 mg). Meperidine consumption in postoperative hours 1 to 12 was significantly higher in the FM group (P=0.02). Postoperative nausea and vomiting (PONV) were more frequent in the FM group (P=0.01). Visual analog scale scores, effective analgesia, Apgar scores, and rates of pruritus and respiratory depression were similar between groups.
• – Conclusions: The intrathecal combination of fentanyl and morphine may provide better perioperative analgesia than morphine alone in caesarean section and could be useful when the time from anesthesia to skin incision is short. However, an increase in PONV and possible acute spinal opioid tolerance after the addition of intrathecal fentanyl warrants further investigation with lower doses of fentanyl.

7. Portable respiratory polygraphy monitoring of obese mothers the first night after caesarean section with bupivacaine/morphine/fentanyl spinal anesthesia. Annette Hein. F1000 Res. 2017 Nov 29;6:2062 .

• – Background: Obesity, abdominal surgery and intrathecal opioids are factors associated with the risk of respiratory compromise. The objective of this study was to study the apnea/hypopnea index the 1st postoperative night in post-cesarean obese mothers under spinal analgesia with bupivacaine, morphine and fentanyl.
• – Methods: Obese pregnant women (BMI >30 kg/m2), ≥18 years, scheduled for bupivacaine/morphine/fentanyl caesarean section with spinal block (subarachnoid) monitored with a portable Embletta/NOX polygraph device on the 1st postoperative night. The apnea/hypopnea index (AHI) was identified using a clinical algorithm and evaluated according to general guidelines; number of apnea/hypopnea episodes per hour: <5 "normal"; ≥5 and <15 mild sleep apnea; ≥15 and <30 moderate sleep apnea; ≥ 30 severe sleep apnea. Oxygen desaturation events were similarly calculated per hour as the oxygen desaturation index (ADI).
• - Results: 40 pregnant women, 27 consented to enter the study, 23 were included, but polysomnography failed in 3. Among the 20 mothers studied: 11 had an AHI <5 (normal), 7 mothers had an AHI ≥5 but <15 (mild OSA) and 2 mothers had an AHI ≥15 (moderate OSA), none with an AHI ≥ 30. The ADI was on average 4.4 and eight patients had an ADI >5. Mothers with high AHI (15.3 and 18.2) did not show a high ADI. The mean SatO2 was 94% (91-96%), and four puerperal women had a mean SatO2 of 90-94%, none with a mean SatO2 <90%.
• – Conclusion: Polysomnography on the 1st post-cesarean night with spinal analgesia with morphine in obese women showed an AHI that in medical terms is considered normal, mild and moderate. Obstructive events and desaturation episodes were commonly out of sync. More studies are warranted looking at preoperative detection of sleep apnea in obese pregnant women, but performing polysomnography prior to delivery or cesarean delivery is complicated and provides little important information.

8. A prospective study of post-cesarean delivery hypoxia after spinal anesthesia with intrathecal morphine 150 mcg. Karim S Ladha. Int J Obstet Anesth. 2017 Nov;32:48-53 .

• – Introduction: Late respiratory depression is a feared complication of intrathecal morphine administration in cesarean section. The incidence, timing, and risk factors for hypoxia in this population are unknown.
• – Methods: Patients undergoing cesarean section with spinal (subarachnoid) analgesia at a tertiary care center from October 2012 to March 2016 were included in the study. The Berlin sleep apnea questionnaire was completed before surgery. Oxygen saturation was recorded every second for 24 hours after the start of spinal analgesia. Desaturation events were defined as a median saturation of <90% (mild) or <85% (severe) over a 30-sec period.
• - Results: 721 patients. 169 women (23%) experienced at least one mild desaturation event, 91 (13%) experienced two or more mild desaturations, and 26 (4%) experienced a severe desaturation event. After intrathecal morphine administration, the median times to first mild desaturation or first severe desaturation were 7.4 (IQR 4.1-13.5) h and 12 (IQR 5.4-19.6) h, respectively. Patients who tested positive for sleep apnea were more likely to have a mild desaturation event (OR 2.31; 95% CI 1.4 to 3.79; P=0.001), as were obese patients (OR 1.80; 95% CI: 1.05 to 3.09, P=0.033).
• – Conclusions: Mild hypoxemia occurred frequently in women who received intrathecal morphine 150 mcg for post-cesarean analgesia.. Desaturations were most frequently observed 4-8 hours after intrathecal morphine administration. Obesity and a positive Berlin questionnaire were risk factors for hypoxemic events.

9. Pruritus after intrathecal morphine for cesarean delivery: incidence, severity and its relation to serum serotonin level. M Aly. Int J Obstet Anesth. 2018 Aug;35:52-56 .

• – Background: Pruritus is the most common side effect of intrathecal morphine, especially in pregnant women. The exact mechanism is unclear and several possible mechanisms have been suggested. Among these is the activation of subtype 3 receptors for 5-hydroxytryptamine (serotonin) by intrathecal morphine.
• – Methods: 40 pregnant women scheduled for elective cesarean section under spinal analgesia were divided into two groups of 20 each in this prospective, randomized study. Both groups received an intrathecal injection of hyperbaric bupivacaine 0.5% (2-3 mL) plus morphine 100 mcg in group 1 (M100) and morphine 200 mcg in group 2 (M200). Two blood samples were taken from each patient to estimate plasma serotonin concentration, preoperatively and four hours postoperatively. After cesarean section, all patients were evaluated for pruritus (incidence and severity), pain (visual analog pain scale), first request for analgesia, and total dose of analgesic in hours.
• - Results: Serum serotonin level increased significantly postoperatively, by 283% vs. 556% (P<0.05) in the M100 and M200 groups, respectively. The incidence of pruritus was 55% in the M100 group and 75% in the M200 group (P=0.32). Postoperative pruritus severity was significantly higher in the M200 group compared to the M100 group (P<0.05) at six and eight hours; but not at other times. Postoperative analgesia, as well as analgesic consumption, was comparable between groups.
• – Conclusion: The level of serum serotonin increased significantly in the postoperative period in both groups, suggesting a role of serotonin in the genesis of intrathecal morphine-induced pruritus.

10. Addition of Fentanyl or High-Dose Morphine to Bupivacaine Is Superior to Bupivacaine Alone during Single-Shot Spinal Anesthesia. Bilge Aslan. Gynecol Obstet Invest. 2020;85(4):312-317 .

• – Background: Single-dose bupivacaine spinal block (subarachnoid, SBP) is a useful technique for pain control during the active phase of labor due to its simplicity and rapid onset. We evaluated the efficacy of adding high-dose fentanyl or morphine to bupivacaine for spinal analgesia.
• – Methods: 90 healthy multiparous women in labor (cervical dilatation ≥7 cm; pain score >4) who requested analgesia. They were randomly assigned into 3 BSA groups: group 1 (n=30) hypobaric bupivacaine 2.5 mg alone; group 2 (n=30) hypobaric bupivacaine 2.5 mg and fentanyl 10 mcg; group 3 (n=30) hypobaric bupivacaine 2.5 mg and morphine 500 mcg. Duration of analgesia, VAS scores, side effects, and obstetric and neonatal outcomes were compared.
• - Results: The gestational age and cervical dilatation of the patients were 38.7 ± 1.5 months and 7.2 ± 2.2 cm (P=0.14 and P=0.65), respectively. The VAS score decreased significantly in all groups at 3 h from the start: from 8.25 to 1.75 in group 1; 7.61 to 1.28 in group 2; 8.12 to 1.26 in group 3 (P<0.001). The duration of the second stage of labor was similar in all groups (45.5, 44, and 38 min, respectively; P=0.67). The total duration of analgesia was significantly longer in group 3 (172, 180, and 190 min for groups 1, 2, and 3, respectively; P=0.01). Fetal Apgar and HR scores were similar in all groups (P=0.95). Side effects were similar, except for itching in group 3 (P=0.01).
• - Conclusion: The addition of high-dose fentanyl or morphine to bupivacaine increases the efficacy and duration of spinal anesthesia (BSA) in the active phase of progressive labor without increasing side effects.

11. Medications for the prevention of pruritus in women undergoing cesarean delivery with Intrathecal morphine: A systematic review and Bayesian network meta-analysis of randomized controlled trials. Yamini Subramani. J Clin Anaesth. 2021 Feb;68:110102.

• – Objective: Intrathecal morphine-induced pruritus can cause significant discomfort in pregnant and postpartum women, and is refractory to conventional antipruritic treatment. This systematic review and meta-analysis evaluated the effectiveness of drugs used for the prevention of intrathecal (IT) morphine-induced pruritus after cesarean section under spinal analgesia. 
• – Methods: Literature search from 1946 to October 2019. All randomized controlled studies (RCTs) comparing drugs used for pruritus prevention with a control group in women undergoing cesarean section under spinal anesthesia with IT morphine were included. The primary outcome examined was the incidence of pruritus within the first 24 hours post-cesarean section.
• – Results: 2594 patients [prophylaxis, n=1603 (62%)  versus control, n=991 (38%)]. These studies investigated 7 drug classes, including serotonin receptor antagonists, dopamine receptor antagonists, opioid agonist-antagonist antagonists, opioid receptor antagonists, histamine receptor antagonists, propofol, and celecoxib. Meta-analysis showed that serotonin receptor antagonist antipruritic prophylaxis [control vs. prophylaxis: 60% vs. 47%; OR (95%): 2.69 (1.43-5.36)] and opioid agonist-antagonist prophylaxis [control vs. prophylaxis: 72% vs. 47%; OR (95%): 4.57 (1.67-12.91)] decreased the incidence of pruritus compared to the control group. Although all included studies were at low risk of bias,
• – Conclusion: This meta-analysis of RCTs shows that serotonin receptor antagonists and opioid agonist-antagonists can prevent postpartum pruritus in the cesarean section with intrathecal morphine compared with the control group. However, more adequately powered RCTs are warranted.