The aim of this integrative review is to identify and appraise the pain management interventions of patients with drug addiction (substance use disorder) admitted in ICUs in order to improve the critical care nurses’ knowledge and performance.

(1) To identify the existing literature that clearly facilitates the evidence-based pain management interventions towards drug-addicted (substance use disorder) patients in ICUs.

(2) To appraise the pain management interventions that do not cause addiction exacerbations to drug-addicted (substance use disorder) patients in ICUs.

We conducted an integrative review of pain management interventions on patients with drug addiction (substance use disorder) admitted in ICUs. Evidence was investigated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.

The population in this study included adult patients with drug addiction (substance use disorder) admitted in ICUs regardless of their gender. The area of interest was pain management approaches towards drug-addicted (substance use disorder) patients.

The intervention in this study was to identify and appraise the evidence-based interventions that will lead to achieve optimal pain relief among drug-addicted patients in ICUs.

What was measured in this study is the achievement of effective pain management interventions towards drug-addicted patients.

In adult patients with drug addiction (substance use disorder) admitted in ICUs, what are the effective interventions for pain management?

This article integrated all peer-reviewed published papers centered on pain management interventions for drug-addicted patients. The electronic databases that were used for the search of peer-reviewed papers included PubMed, Cochrane Library, Web of Science, Ovid Medline, EMBASE and Google Scholar. The following keywords were used for search in electronic databases as follows; ((“Pain management”) AND (patients)) and (drug addiction)). All search results, including title and abstract, were entered into Endnote-7 software. English articles on pain management with a target group other than addicted patients were excluded. At first, the search outcome was imported into Endnote (n=62). By eliminating duplicate articles, abstracts of 40 studies were screened. In case of any ambiguity in the abstract or the title, the full text of the study was downloaded and reviewed by two authors. Once ambiguity was cleared, the study was then further screened; otherwise, it would be eliminated from the study. Ultimately, according to the inclusion and exclusion criteria, 12 studies remained and were further screened for quality and inclusion in the study.

a. The full text of these studies was assessed with PRISMA. All 12 studies were scored separately by two authors. In case of any disagreement, the points were discussed until the consensus was reached. Finally, 4 original articles were included in the study (Fig 1).

Fig. (1). Flow chart of studies included in the integrative review.

Two independent authors extracted data on study design and year of publication of all articles published in peer review journals in English from 2010 to 2019, their sample size and findings. The reasons for the exclusion of articles have been explained above. One study was performed by a nurse [12]. We used Joanna Briggs (JBI, 2017) appraisal tool to appraise the articles. JBI’s critical appraisal tools assist in assessing the trustworthiness, relevance and results of published papers. The checklist for analytical case report studies has 8 questions and 13 questions for Randomized Control Trial studies. All studies were reviewed by two authors and if there was found a disagreement, the articles were again reviewed.

This research was approved by the ethics committee of Tehran University of Medical Sciences (No: 98-3-163-45742).

Data was presented in the form of a narrative. Meta-analysis was not possible due to the heterogeneity of clinical results that was found in small-scale trials included in this integrative review.

Rafiei et al. (2013) revealed that nursing sedation and pain management protocols for opium addicted critically ill patients must be well implemented in an attempt to enhance pain management. This could lead to adequate pain relief among addicted patients, and it also reduces exacerbations. The study demonstrated that the effective implementation of nursing sedation and pain protocols among opium-addicted critically ill admitted in ICU will reduce the accumulation of sedative drugs and antipain medication. Noteworthy, it will minimize and reduce the severity of pain among opium-addicted patients [12].

In this study, Richmond Agitation Sedation Scale (RASS) and Behavioral Pain Scale (BPS) were used to assess the pain and sedation levels in opium-addicted patients hospitalized in ICU. During the admission of patients, the mean score of the RASS was -1.74 +/-1.1 in group 1 where nursing protocols were implemented and it was -1.81+/-1.1 in group 2 where no protocols were applied. But after hospitalization in ICU, the mean score of the RASS was -1.10+/-1.0 in group 1 where nursing protocols were implemented and -1.63+/-1.1 in group 2 where no protocols were applied. Regarding BPS during admission, the mean score in groups 1 and 2 was 7.9+/-1.3 and 8.0+/-1.6, respectively. After hospitalization, the mean score for PBS was 5.8+/-1.6 in group 1 and 6.9+/-2.1 in group 2 [12].

Henceforth, these findings revealed that patients in group 1 where nursing sedation and pain protocols were implemented received a smaller dose of morphine and midazolam compared to group 2 patients where no protocols were applied. The strength of this study was that patients with a past medical history of kidney, lung, heart and liver were excluded from the study to avoid deterioration and further injuries. But one weakness was that this study recruited only surgical related patients and also included a small sample size (n = 37) [12].

Griffin et al. (2016) demonstrated that Buprenorphine-naloxone therapy with counseling in opioids dependent patients produced the desired outcome of optimal pain relief. The study took a period of 12 weeks involving opioids dependent patients. The aim of the study was to investigate the effect of Buprenorphine-naloxone therapy on opioids dependent patients. The dose of 8-32mg of Buprenorphine prescribed by physicians was administered to opioid dependent patients. All heroin dependent patients for more than one month with ≥ 18 years were recruited in the study.

The finding demonstrated that the severity of pain was associated with the increase in the dose of opioids among patients. In addition, the study confirmed that the administration of Buprenorphine-naloxone therapy provide good clinical results with respect to pain relief among opioid addicted patients. The study was conducted among racially homogeneous individuals in United States and found to be effective in relieving pain. They also explained that treating pain in addicted patients is still a challenge among critical care nurses; hence this leads to adverse effects such as chronic pain and delirium in critically ill patients because their pain intensity is underestimated and undertreated [13].

The strength of this study was that the patients with mental illness were excluded from the study to avoid further exacerbations or deterioration of their condition, while the weakness was that the study’s duration was a long period of 4-12 weeks hence this could lead to more adverse effects in the patients.

Noteworthy, the study by Imani et al. (2011) evaluated the analgesic effects of adding chlorpromazine, clonidine, promethazine and midazolam in morphine infusion. This study recruited post-operative orthopedic patients with drug addiction disorders. The patients involved in this study were 90 addicted patients. These patients were distributed into three groups. Group 1 received 20mg of morphine sulfate + 50mg of promethazine+10mg of midazolam. Group 2 received the same dose as group 1 + 150mg of clonidine. Group 3 received only 40mg of morphine [14].

The study demonstrated that pain management among addicted patients had been difficult as these patients possessed another health issue apart from having pain. The study findings showed that instead of increasing the morphine dose, it is better to add promethazine, clonidine, chlorpromazine and midazolam in the morphine infusion. This is due to the strength of this analgesics cocktail that most addicted patients were more satisfied with the analgesic effect of these medications on optimal pain relief [14].

The strength of this study was that the combination of these analgesics drugs including clonidine, chlorpromazine, promethazine, midazolam and morphine showed a good response to pain relief and increased satisfaction of addicted patients. However, the weakness was that the study did not recruit female patients.

Finally, Kouchek et al. (2013) evaluated the intravenous paracetamol therapeutic effect and its adverse reactions in contrast to fentanyl among ICU patients with mild to moderate pain. The Visual Analogue Scale (VAS) was used for pain assessment before the administration of analgesics. In 1^st group, intravenous paracetamol 1gm was given every 6 hours for 48 hours, while in the 2^ndgroup, intravenously fentanyl 25μg was given every 3 hours for 48 hours. The participants included were managed for any adverse effects involving the central nervous system and liver. The clients’ age, sex and pain level were coordinated in both the groups [10].

During the first 24 hours, the pain score was 2.60 (+/-1.2) and 2.40 (+/-1.5). After 48 hours, the pain score was 2.25 (+/-0.96) and 2.05 (+/-1.1) in paracetamol and fentanyl groups, independently. Henceforth, the results demonstrated that the therapeutic effects of intravenous paracetamol and fentanyl on pain relief were the same. The study revealed that the administration of intravenous paracetamol is safer and effective for treating mild to moderate pain among opioid addicted patients as it minimizes and reduces the dependence of opioids administration in ICUs. Subsequently, the study emphasizes the use of midazolam for sedating patients in order to decrease the use of opioids to achieve sedative effects [10].

The strength of this study was that the severity of patients’ pain was diagnosed and scored before drug administration. In addition, laboratory investigation was done to protect the liver from injury as frequent paracetamol use leads to liver failure. Regarding the weakness, the scale used for pain assessment was not suitable for diagnosing pain in ICU patients (Visual Analogue Scale). Instead, the tools like behavioral pain scale (BPS) and critical care pain observation tool (CPOT) could have been used [15].

The hierarchy of evidence is a foundation key of evidence-based practice, especially when looking for effective interventions towards clinical problems. In this integrative review, we only included RCTs as they are considered to be the highest on the hierarchy of evidence to answer intervention questions. In addition, we assessed the hierarchy of evidence using the Joanna Briggs Institute (JBI) criteria in order to find the scientific studies to be included in our integrative review which was found to be located on Level 1 as shown in Table 2 [17].

Due to clinical heterogeneity of the findings and weaknesses as mentioned in Table 3, and the smallest sample sizes recruited in RCTs, this integrative review was insufficient to meet the criteria of being used as a reference for the effective approaches to pain management among critically ill addicted patients admitted in ICUs [18]. Even though the four (4) RCTs included in this review demonstrated the highest hierarchies of evidence according to JBI critical appraisal tools [19], but still this integrative review cannot be considered as the gold standard approach to be implemented by health practitioners in clinical practice.

All randomized controlled trials included in this integrative review reported adequate information required for assessment. These were concealment of allocation to treatment groups, analysis of the participant groups and the blinding fashion. However, two clinical trials applied double-blinded and the other two studies used single-blinded studies. In double-blinded studies, both participants and experimenters were not aware of the treatment allocation but in single-blinded studies, only participants were not aware of the treatment allocation. All these principles were applied to avoid allocation biases that can arise between researchers and participants [19].

There was no selection bias in the RCTs recruited in this integrative review due to the effective concealment of allocation that was implemented. Allocation concealment was implemented when the participants entered the trial (during recruitment) in all RCTs that were included in this review. Furthermore, RCTs were included in this review because it is the gold-standard design that is used to appraise effective therapeutic interventions but also it has the highest quality of evidence (Level 1b) as shown in the criteria used for selection of studies based on the level of evidence (Table 2) above [18, 19].

All of the studies included in this review provided the takeaway lesson; the age of the respondents who were recruited and the inclusion and exclusion criteria were mentioned. Some of the interventions that were reported as evidence-based in improving the pain management of drug-addicted (substance use disorder) patients included effective implementation of the nursing sedation and pain protocols, implementation of Buprenorphine-naloxone therapy, administration of morphine in combination with other drugs including chlorpromazine, clonidine, promethazine and midazolam, and utilization of intravenous paracetamol.

This integrative review included resources that were published in peer-reviewed journals from 2010 to 2019. Therefore, gray materials, review articles, commentaries, editorials and articles presented at seminars and conferences were wasted and not included in the review.

Also, this integrative review was faced with a scarcity of published and unpublished resources or relevant papers that address the pain management approaches towards addicted patients in ICUs. Most of the studies focused on pain management in drug-addicted (substance use disorder) patients without classifying their clinical settings. Hence there was found inadequacy of effective pain management approaches to be added in this integrative review.

Finally, the studies included in this review involved a small sample size, hence this factor limited generalization to other clinical settings. However, the findings produced were rich in information on pain management approaches to drug-addicted patients admitted in ICUs. This limitation is similar to that of the study by Kukull and Ganguli [20].