The Effect of Continuous Subcutaneous Infusion of Chlorpromazine on Refractory Delirium in Advanced Cancer: Retrospective Study

Context: Delirium in cancer is often difficult to control and refractory when haloperidol is invalid which is considered standard therapy. We need second and subsequent-line therapy to reduce hyperactivity and not to over-sedation for refractory delirium. Objectives: To investigate the efficacy and safety of continuous subcutaneous infusion chlorpromazine on delirium refractory to first-line antipsychiatric medications in advanced cancer palliative care setting. Method: The study population consisted of patients who received continuous subcutaneous infusion chlorpromazine for delirium at two certified PCU. Primary endpoint was the proportion of patients who showed improvements in delirium severity by Delirium Rating Scale Revised 98 score of less than 13 or decrease from baseline and maintained the ability to communicate coherently by Communication Capacity Scale Item-4 score of 2 or less. Secondary outcome were the Nursing Delirium Screening Scale subscale score, and injection site reactions evaluated according to the Common Terminology Criteria for Adverse Events. These outcome measures were assessed at baseline, 48 hours and 7 days after the start of the study. Result: Among eighty-four patients, sixty were positive responders (71.4%, 95% CI [61–80]). The mean CCS Item-4 scores significantly decreased from the baseline value of 1.48 (range 0–3) to 1.03 (range 0–3) at post-treatment (p<0.001). Grade 2 or higher injection site reactions were observed in 1 patient (1.2%, 95% CI [0–7]). Conclusion: Our study suggested that continuous subcutaneous infusion chlorpromazine could improve refractory delirium symptoms and patients’ communication capabilities. Although most of the skin disorders observed in association with chlorpromazine were mild, their incidence rates were relatively high, suggesting the need for careful monitoring.

Frequency of Serious Adverse Skin Reactions Caused by Continuous Subcutaneous Administration of Psychotropic Drugs

Continuous subcutaneous injections of medication are effective in controlling symptoms of the terminal stage of cancer. Chlorpromazine and levomepromazine occasionally cause skin irritation. We examined all patients who underwent continuous subcutaneous administration of psychotropic drugs (chlorpromazine, levomepromazine, midazolam) at the palliative care unit of our hospital from April 2010 to March 2013, the frequency of adverse skin reactions of Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 3 or above. Of the 603 hospitalized patients, 389 (64.5%) underwent continuous subcutaneous administration of one of the three drugs. The frequency of grade 3 or above (ulceration or necrosis) adverse skin reactions was 4 out of 345 chlorpromazine cases (1.2%; 95% CI: 0.0-2.3%), 2 out of 90 levomepromazine cases (2.2%; 95% CI: −0.8-5.2%), and 0 out of 210 midazolam cases (0.0%; 95% CI: 0.0-0.0%). The frequency of serious adverse skin reactions caused by continuous subcutaneous administration of psychotropic drugs was low, suggesting that this treatment is relatively safe for the skin.

Usefulness of stepwise opioid switching to methadone: a case report

<b>Introduction:</b> The use of methadone in Japan is limited to cases being switched from the preceding use of strong opioids; the stop-and-go strategy is recommended in which the previously used opioid analgesic is discontinued and methadone is initiated at its full estimated dosage. <b>Case:</b> Refractory cancer pain due to an iliolumbar syndrome was temporarily exacerbated by the stop-and-go switching to methadone from morphine along with ketamine. Pain relief was achieved upon readministration and concomitant use of morphine with methadone after approximately two weeks. <b>Discussion:</b> Through examining this case, we believe that a stepwise switching strategy, rather than the stop-and-go strategy, could be more useful. Considering that overdosage may cause side effects, it is safer to initiate methadone with a small dose. However, more studies need to be conducted to decide whether the establishment of the initial dosage and dosage adjustment should be made more flexible to avoid pain intensification. Further investigation is required on whether the concomitant use of adjuvant analgesics such as ketamine, which similar to methadone is an NMDA receptor antagonist, should be continued when switching to methadone.