Low dose ketamine reduces pain perception and blood pressure, but not muscle sympathetic nerve activity, responses during a cold pressor test

Pain is highly prevalent among people with cancer and often remains undertreated despite conventional management, with the World Health Organization estimating that 55–66% of patients experience greater-than-moderate pain even when managed in specialist units. Opioids are the standard therapy for cancer pain but carry a narrow therapeutic window, problematic side effects (for example nausea, constipation, sedation, neuroexcitation) and the potential for escalating doses due to tolerance and opioid-induced hyperalgesia. This clinical challenge motivates interest in non-opioid adjuvants. This paper reports a single-patient case study in which low-dose ketamine (LDK) infusion was used as an adjunct to high-dose opioid therapy for refractory cancer-related pain. The study aims to describe the protocol, monitor analgesic efficacy and opioid-sparing effects, and record adverse events and vital signs during and after the infusion period, with follow-up of pain scores and opioid use for 30 days after treatment.

This report is a single-case, observational study carried out under institutional review board approval in a palliative care setting. Patel and colleagues describe a 55-year-old male with metastatic prostate cancer (Gleason 9) and severe mixed neuropathic and somatic pain from bone metastases, who was receiving multiple concomitant medications including high-dose opioids totalling 458.8 morphine milligram equivalents (MME) per day. The patient had multiple comorbidities (including atrial fibrillation, hypertension, obesity and sleep apnoea) and prior limitations on non-steroidal anti-inflammatory use. The intervention followed a local LDK protocol (<0.5 mg/kg) established in 2019. The infusion formulation was ketamine (100 mg in 100 mL D5W, 1 mg/mL) with a maximum push dose of 50 mg over 1 minute. The active infusion described in the case was a 3-day titration: 0.1 mg/kg/hr on Day 1, 0.2 mg/kg/hr on Day 2, and 0.3 mg/kg/hr on Day 3. Pain was assessed with the Numerical Rating Scale (NRS), recorded every 4 hours while on infusion, and observational data collected within the first 24 hours of infusion on pain characteristics, vital signs, respiratory depression, tolerance and satisfaction. Opioid consumption (MME) and pain intensity were compared for the 30 days before, during and for 30 days after the ketamine infusion. The extracted text notes some inconsistency about duration (a 3-day infusion protocol is described in Methods while the Discussion refers to a 5-day period), and the exact duration of post-infusion monitoring is 30 days for pain and opioid use comparisons. The patient subsequently died and the authors report that informed consent could not be obtained because next of kin were untraceable.

Before ketamine, the patient consistently reported severe pain (9/10 on the NRS) while receiving an equianalgesic opioid dose averaging 458.8 MME/day. During the described LDK titration, the patient reported a reduction in pain to an average of 5/10 on the NRS. This improvement coincided with a reported 32.43% reduction in overall opioid use during the infusion period. Over the 30 days following the ketamine infusion, average pain was reported as 4.75/10, which the authors describe as approximately a 50% reduction from baseline. Opioid prescribing changes after the infusion included a reduction to 310 MME/day overall, cessation of transdermal fentanyl and a 16.67% reduction in methadone use (as reported by the authors). No ketamine-related adverse effects commonly associated with higher doses (for example hallucinations or marked agitation) were reported in this patient. The authors state that no additional adverse events were noted. Vital signs and respiratory status were monitored during infusion, but the extracted text does not provide detailed numerical data on those measures in the Results section beyond noting monitoring and no recorded complications. The text also reports an observed improvement in the patient's mood after infusion, with a nurse note describing the patient as being in “great spirits.”

Patel and colleagues interpret the case as illustrative of the potential utility of low-dose ketamine as an adjunct to opioids in palliative care for refractory cancer pain. They situate their findings within broader concerns about under-treatment of cancer pain and the harms of escalating opioid therapy, and note that LDK may both reduce pain intensity and allow opioid sparing. The authors discuss mechanistic rationale: ketamine is an NMDA receptor antagonist that can reduce central sensitisation to pain and may potentiate opioid receptor effects, thereby prolonging opioid-induced analgesia. They also raise the possibility that ketamine's anti-depressive effects might contribute to perceived pain relief, suggesting an emotional component to its analgesic action. The authors acknowledge the limited evidence base: prior studies they cite are small, heterogeneous in intervention and outcome measures, and do not yet establish optimal titration regimens. They note the single-case nature of their report and implicitly that generalisability is limited. Safety data are limited to this one patient, who did not experience reported psychotomimetic side effects, but the authors call for further titrated dose trials across pain scenarios to better characterise efficacy and safety. Ethical constraints are described: the patient died and informed consent could not be obtained from next of kin despite attempts, which the authors disclose as part of study limitations. Finally, they suggest that LDK warrants further investigation as a potentially simple and effective adjunctive analgesic in palliative settings, while emphasising the need for additional research to determine efficacy, dosing schedules and administration routes.

This single, selective case suggests that intravenous low-dose ketamine infusion (<0.5 mg/kg) used as an adjunct to high-dose opioids was associated with meaningful short-term reductions in pain scores and opioid requirements in a patient with advanced metastatic prostate cancer. Patel and colleagues argue that, although promising, these observations require confirmation in larger, controlled studies to define optimal dosing and to establish safety and generalisability in palliative care populations.