In this randomized control trial, we examined the role of acupuncture as an integrative treatment to help manage sleep disturbances in multiple myeloma patients undergoing HSCT. Our data suggest that true acupuncture may significantly improve sleep efficiency in this population, especially in the inpatient setting. Our results also showed a trend that acupuncture can noticeably improve sleep-onset latency time in this population despite not achieving statistical significance.
One of the strengths of our study is that our study was in a population of cancer patients known for their high symptom burden. Most of the previous studies of acupuncture on insomnia were conducted on non-cancer patients [30]. Only a few studies included insomnia patients with comorbidities such as stroke, end-stage renal disease, perimenopause, pregnancy, and psychiatric diseases [30]. A few studies investigated the effect of acupuncture on sleep quality in cancer patients. In a systematic review conducted by Choi et al in 2017, 6 studies investigated the effect of acupuncture on insomnia in cancer patients[30]. It was not clear whether acupuncture has a similar effect in an acutely ill population who experience complex symptom clusters. HSCT preceded by high dose chemotherapy causes significant acute side effects, including pain from mucositis, poor appetite, fatigue, disturbed sleep, nausea, vomiting, and diarrhea[4, 31], which contribute or exacerbate insomnia. Our study suggests acupuncture can have an effect in this clinical setting.
Because acupuncture can reduce some the symptoms, such as pain, nausea, and vomiting [14, 32], we are not sure if acupuncture improves sleep quality directly or indirectly by reducing contributing symptoms, as our previous manuscript showed that acupuncture can reduce these symptoms. This can be something interesting to investigate in future studies.
Subgroup analysis showed that the significant improvement in sleep efficiency persisted in inpatients only. Within outpatients, there were no significant changes between the two arms. The decision to treat a patient in the inpatient setting was provider and patient dependent. Usually, choosing a patient setting is made due to lack of a caregiver for outpatient transplantation or the presence of an existing comorbidity that requires close monitoring (i.e. renal disfunction). It is well known that inpatients are more likely to experience sleep disrupting factors during their hospital stay, which include noise from visitors and medical staff nearby, excessive light exposure, unfamiliar surroundings, night vital sign checking, and blood drawing [23, 24]. These factors commonly disrupt normal circadian rhythm leading to a decrease in sleep quality [33, 34]. Studies suggest that even if the total number of sleep hours in a day can approach normal at the hospital, half of sleep occurs during daytime and in interrupted short intervals[33, 34]. Patients in the inpatient setting might have received more medications that could influence sleep such as antiemetics or sleep aids. Our results show that acupuncture may have a stronger effect in the inpatient setting.
Another strength of our study is that we used sham acupuncture, instead of usual care, as control In the systematic review conducted by Cheuk et al., among 15 studies with needle acupuncture as an intervention, only 3 of those studies included sham as a control [35]. However, none of these studies had proper blinding or allocation concealment. Two out of the three studies had a moderate to high attrition bias. In contrast, our study was properly blinded. At the end of our study, effectiveness of blinding was assessed by asking patients to guess their allocation. Patients had a 50% chance of getting the right answer. Our loss to follow up rate was low (4.8%). Therefore, our data adds to the existing limited evidence by providing data collected from a well blinded and low attrition study.
Acupuncture was safe with minimal attributable adverse events. These findings may suggest that acupuncture has the potential to help manage sleep disturbances in patients undergoing HSCT without adding more burden or serious adverse effects during the procedure.
A few limitations were present in our study. First, our study had a small sample size. This study was powered to estimate the effect size of acupuncture on symptom burdens, not to definitively prove the efficacy of acupuncture by rejecting a null hypothesis. The second limitation is that sleep quality was a secondary outcome. Secondary outcomes or confounding variables could have led to a false discovery. Secondary findings need to be interpreted and require further verification. To verify these findings, a larger trial should be conducted. Another limitation is that a usual-care control group was not included. Usual care control would give us info on real world effect size as in clinical practice. Our study’s generalizability is also limited. We did not include allogeneic HSCT patients because their course is too heterogeneous for a study of a small sample size.
Despite the limitations, to our knowledge this is the first randomized controlled trial examining acupuncture as an integrative approach for improving certain aspects of sleep in the HSCT setting. Future studies will shed more light on the effect of acupuncture on sleep quality in patients who are acutely ill, especially those admitted to a hospital.