Oral Herpes Simplex Reactivation After Intrathecal Morphine: A Prospective Randomized Trial in an Obstetric Population

Abstract

There is now evidence for an association between the use of epidural morphine and reactivation of herpes simplex labialis (HSL). There are no studies that definitively demonstrate the relationship between HSL reactivation and spinal intrathecal morphine. To investigate this relationship, we randomized and prospectively studied 100 obstetric patients with a history of HSL undergoing cesarean delivery under spinal anesthesia. One group received intrathecal morphine plus IV morphine via patient-controlled analgesia (ITM+PCA group) for postoperative analgesia, and a second group received only IV morphine via patient-controlled analgesia for postoperative analgesia (PCA-only group). Patients were followed for a 30-day period. In the ITM+PCA group 19 (38%) patients had HSL reactivation whereas eight (16.6%) had HSL reactivation in the morphine PCA-only group (P = 0.028). The incidence of pruritus in the ITM+PCA group was also more frequent in the early postoperative period. Our data show HSL reactivation in both the ITM+PCA group and PCA-only morphine group, with a more frequent incidence in the ITM+PCA group.

Acute Morphine Administration Reduces Cell-Mediated Immunity and Induces Reactivation of Latent Herpes Simplex Virus Type 1 in BALB/c Mice

“…Opiates have been found to have many physiological and immunological effects that influence the pathogenesis of infectious diseases (17). In humans, it has been reported that morphine administration induces reactivation of latent herpes simplex labialis (8). In this paper we showed that acute morphine administration, similarly to hyperthermic stress, reduces CTL responses, lymphocyte proliferation, and IFN- production and induces reactivation of latent HSV-1 in a mouse model.…”

“…Our previous work has shown that acute morphine administration increases mortality during HSV-1 infection in BALB/c mice (7). In humans, morphine administration induces reactivation of latent herpes simplex labialis (8). Recurrent HSV-1 ocular disease results from reactivation of the latent virus in the trigeminal ganglia, often following immunosuppression or exposure to a variety of psychological or physical stressors.…”

Neuraxial Morphine and Oral Herpes Reactivation in the Obstetric Population

“…To clarify whether intrathecal morphine specifically increased the risk of reactivation versus systemic opioids, Davies et al 30 designed a randomized controlled trial that included women with a reported history of HSV-1 scheduled for elective cesarean delivery under spinal anesthesia. This trial confirmed an increased risk of reactivation with intrathecal morphine.…”

“…However, clinicians are understandably concerned about the risk of HSV transmission to the neonate whose mother has a recurrence. 27,28,30 …”

Acute Morphine Administration Reduces White Blood Cells’ Capability to Induce Innate Resistance against HSV-1 Infection in BALB/c Mice

“…Consistent with these findings, opioid administration has been associated with increased susceptibility of animals to microbial infection [15] . It has been proven that morphine alters the course of HSV-1 infection [16,17] . Furthermore, morphine reduces the activity of immune cells, including NK cells and macrophages, and decreases the production of cytokines like IFN-␥ and IL-12 [18][19][20] .…”