A Perspective on Hypercapnia Events After Cesarean Delivery in Women Receiving Intrathecal Morphine

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We read with interest the well-conducted study by Bauchat et al1 in which the authors prospectively measured transcutaneous carbon dioxide (CO2) in women after cesarean delivery who received intrathecal morphine for postcesarean delivery analgesia. The authors reported a 32% (99% confidence interval, 2%–45%) incidence of hypercapnia events, defined as transcutaneous CO2 > 50 mm Hg ≥ 2 minutes, with a median (interquartile range) number of events of 3 (1–6) per woman. We commend the authors for undertaking this study and providing their detailed results. However, we feel that it is important to provide additional perspective on their study findings.
First, the authors equate transcutaneous hypercapnia to respiratory depression, despite no corresponding change in respiratory rates. We acknowledge that many definitions of postoperative respiratory depression have been applied,2 including the hypercapnia definition used in their study. Bradypnea (respiratory rate < 10 bpm) is the one most commonly applied in the postoperative setting.2 Hypercapnia alone without reference to respiratory rate may be misleading. Terms such as bradypnea, hypoxemia, and hypercapnia are more illustrative yet do not necessarily imply respiratory depression or a depressed ventilatory response.
Second, their finding of a 5 mm Hg (99% confidence interval, 2–8 mm Hg) difference in CO2, after versus before cesarean delivery, is likely not clinically significant. Over 1.4 million cesarean deliveries are performed annually in the United States, and the vast majority of these women receive intrathecal morphine.3 There are no reports of respiratory depression among women receiving intrathecal morphine for cesarean delivery reported in meta-analysis of prospective studies,4 nor in large registries including the Anesthesia Closed Claims Project. Retrospective studies report a very low incidence (<1%) of clinically insignificant respiratory depression.5 If one-third of the women who received intrathecal morphine for postcesarean delivery analgesia had clinically significant respiratory depression in the setting of generally busy postpartum floors, where monitoring may be inconsistently applied, would there not be frequent reports of maternal harm? Despite a 32% incidence of hypercapnia in the study by Bauchat et al,1 no women required oxygen therapy or naloxone. There was only an isolated episode of bradypnea and no significant sedation. These observations suggest these events are trivial and not clinically significant. Additionally, the observation that the hypercapnia events were episodic and not associated with a steady rise in CO2 suggests that they were more related to position changes or artifacts than to a depressed ventilatory response induced by intrathecal morphine.
Third, the authors suggested that intrathecal morphine caused the observed hypercapnia. However, without a control group that did not receive intrathecal morphine, it is impossible to exclude other factors that affect respiratory dynamics. Postpartum pain associated with cesarean delivery and postoperative sleep positions may decrease tidal volume and produce hypercapnia. Cesarean delivery and peripartum sleep deprivation may worsen preexisting or pregnancy-related obstructive sleep apnea and sleep-related hypercapnia or hypoxemia. Normalization of pregnancy-related respiratory physiology may also generate rising CO2 levels postpartum. Additionally, most women also received systemic opioids.
We hope that the reported high incidence of clinically insignificant hypercapnia events in this study by Bauchat et al1 does not lead to the abandonment of intrathecal morphine for cesarean delivery. Intrathecal morphine is recommended over parenteral opioids due to improved analgesic efficacy6 and reduced respiratory depression risk relative to parenteral opioids.5 Low-dose intrathecal morphine provides high-quality postcesarean delivery analgesia, is recommended by the Society for Obstetric Anesthesia and Perinatology,6 and has been safely and effectively administered for decades to millions of women undergoing cesarean delivery.

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