Intrathecal Drug Delivery System in Prepontine Cistern for Patients with Intractable Craniofacial Cancer Pain: A Multicenter Retrospective Study

Abstract

Background: Patients with craniofacial cancer frequently suffer from severe pain. The traditional intrathecal, oral, or intravenous analgesics could only provide insufficient pain relief with many side effects. Thus, a more effective analgesia approach is required. This study aimed to investigate the safety and efficacy of placing the catheter of an intrathecal morphine pump in the prepontine cistern for the treatment of craniofacial cancer pain.

Methods: We performed a retrospective study of patients with primary or metastatic craniofacial cancer pain who received the catheter placement of an intrathecal morphine pump into the prepontine cistern in eleven medical centers from September 2019 to December 2023. Friedman test and pairwise signed-rank test were used to evaluate the difference in numeric rating scale (NRS) scores, the number of breakthrough pain episodes, dose of intrathecal morphine, and dose of systemic morphine equivalents (oral, patch, intravenous) from preoperative period to postoperative days 1, 7, and 30. P values were corrected for multiple comparisons using Bonferroni test.

Results: The study included 33 patients. The median (interquartile range [IQR]) of NRS scores at days 1, 7, and 30 postimplant were 2.0 (1.0-3.5), 2.0 (1.0-2.0), and 1.0 (1.0-2.0), respectively, which was significantly lower than that before surgery (median, 8.0; IQR, 7.0-10.0; all P < .001). Compared to baseline number/d of breakthrough pain episodes (median, 6.0; IQR, 4.5-10.0), there was a progressive decrease in the number/d of breakthrough pain episodes at day 1, day 7, and day 30 postimplant, and the median (IQR) were 1.0 (0.0-3.0), 2.0 (0.0-3.0), and 0.0 (0.0-1.2), respectively (all P < .001). Approximately 78.8% and 96.7% of patients reported pain relief >50% at days 1 and 30 postimplant, respectively. Compared with that at day 1 postimplant, the proportion of patients with a pain relief rate >75% at day 30 postimplant also increased with continued intrathecal treatment. Compared to the dose of baseline systemic morphine equivalents (median, 228 mg.d -1 ; IQR, 120-408 mg.d -1 ), the dose of systemic morphine equivalents reduced significantly from 0(0-120) mg.d -1 at day 1 postimplant ( P = .001), to 0 (0-0) mg.d -1 at days 7 and 30 postimplant (both P < .001). Few patients reported perioperative adverse events, including nausea, constipation, hypotension, urinary retention, dry mouth, headache, and sedation. No severe adverse events occurred.

Conclusions: Placing the catheter tip of an intrathecal morphine pump into the prepontine cistern could effectively relieve refractory craniofacial cancer pain with an extremely low total morphine dose requirement and few adverse events. This procedure could be considered in patients with severe refractory craniofacial cancer pain.

Graphical abstract

Figure 1.

Imaging of a correctly placed intrathecal catheter. A, A fluoroscopy to confirm the intrathecal catheter path and the position of the intrathecal catheter tip. The long red arrows indicate the intrathecal catheter. The short red arrow indicates the tip of the catheter. The red rings indicate the foramen magnum. B and C, the skull base and coronal plane of a 3D CT reconstruction showing the catheter passing through the foramen magnum and entering into the prepontine cistern (the hollow red arrow). CT indicates computed tomography.

Figure 2.

Reduction in NRS scores through time postimplant. Boxes represent interquartile range. The central lines represent the median. Whiskers represent minimal and maximal values. The dot represents an outlier. Statistical differences were obtained by performing pairwise comparisons after a significant Friedman analysis of variance. Asterisks indicate statistical significance compared with baseline (***P < .001 after Bonferroni correction for multiple comparisons). NRS indicates numeric rating scale.

Figure 3.

Analgesic outcomes, morphine dose, and perioperative adverse events. A, Reduction in the number of breakthrough pain episodes through time postimplant. B, The number of patients who experienced pain improvement at days 1 and 30 postimplant. C, Morphine dose over the study period. D, Number of patients with perioperative adverse events. Boxes represent interquartile range. The central lines represent the median. Whiskers represent minimal and maximal values. The dot represents an outlier. Statistical differences were obtained by performing pairwise comparisons after a significant Friedman analysis of variance. Asterisks indicate statistical significance compared with baseline (**P < .01, ***P < .001 after Bonferroni correction for multiple comparisons).

Figure 4.

NRS scores and morphine dose based on cancer type and pain location. NRS indicates numeric rating scale.

Figure 5.

Anatomic diagram of the pontine cistern and cranial nerves in a cadaver (donated by the Department of Human Anatomy, Nanjing Medical University). A, A sagittal bitmap of the pontine cistern and its surrounding structures. The pontine cistern is located on the ventral side of the pons (the red arrow). B, An oblique lateral bitmap of the brain showing the exit points of cranial nerves. Cranial nerve IV, known as the trochlear nerve, and cranial nerve XII, referred to as the hypoglossal nerve, are both located ventrally and not depicted in the diagram.