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INTRODUCTION
Traumatic brain injury (TBI) is a major health issue worldwide and refers to any disruption in brain function or detectable brain damage resulting from an external impact [1]. In 2019, approximately 27.16 million new cases of TBI occurred globally, resulting in 7.08 million life years of functional impairment [2]. The outcomes of TBI range from full recovery to lifelong disability or death [3], and the effects of TBI are disproportionately higher in low- and middle-income countries (LMICs), which bear approximately 90% of all injury-related fatalities. According to the World Health Organization, TBI is responsible for nearly half of these fatalities. The incidence of TBI in LMICs is estimated to be three times higher than that in high-income countries [4].
In conflict-affected settings, such as Northwest Syria, the burden of TBI is even more pronounced, exemplifying how armed conflict can severely disrupt the healthcare system and population health. In Northwest Syria, since the conflict began, life expectancy has dropped by 27%, with 6% of the population dying directly from the war [5]. Reports have indicated that brain injuries are the most common form of trauma during this conflict [6].
Healthcare infrastructure in such resource-limited settings is often inadequate, and patients with TBI are typically managed in general wards with basic, intermittent vital sign monitoring instead of continuous or invasive methods such as intracranial pressure (ICP) monitoring or advanced cardiorespiratory support [7,8]. In the absence of continuous monitoring, frequent manual checks and regular sedation reassessments with dose adjustments based on clinical responses are recommended. Moreover, non-pharmacological interventions such as communication, quiet environments, family presence, and structured sleep support can help reduce agitation in intensive care unit (ICU) patients, including those with TBI [9].
Critically ill patients with TBI often experience agitation, anxiety, confusion, and pain, which are worsened by ICU stress and immobility, necessitating multimodal pharmacological and non-pharmacological interventions [10]. Sedation provides neuroprotection, reduces the ICP, prevents secondary injury, controls agitation, facilitates mechanical ventilation, and reduces seizures and physiological stress [11-13]. According to the Society of Critical Care Medicine (SCCM) guidelines [9], regular pain and sedation assessments should be performed for all critically ill patients, with medication titration aimed at maintaining light sedation unless contraindicated. Sedation scales have been developed to guide titration.
In critical care settings, the Richmond Agitation-Sedation Scale (RASS) is widely used to monitor sedation status, and its reliability has been validated by Ely et al. [14] and Sessler et al. [15]. The present study aimed for an RASS target range of –2 to +1 to accommodate the specific clinical and neurological requirements of patients with TBI [16], which corresponds to light sedation, aligned with the recommendations outlined in the pain, agitation, and sedation management guidelines [9].
Nurses play a crucial role in sedation management, particularly in critical care, overseeing continuous patient assessment and medication administration [17]. However, evidence shows that ICU nurses often underuse standardized pain and sedation tools for non-communicative patients and may lack guideline awareness, resulting in suboptimal care [18]. Thus, the regular use of assessment scales such as the RASS is vital to enhance nurses’ decision-making and ensure safe sedation [17]. Standardized agitation assessments can also help identify non-pharmacological distress factors and improve analgesia and comfort [19]. Despite these established recommendations, sedation scales have not been fully validated for patients with TBI, who present unique challenges in sedation and agitation assessment. The application of findings from other critical care populations may lead to inappropriate sedation. Moreover, while nurse-led protocols are effective in well-resourced ICUs, their influence in resource-limited settings such as Northwest Syria remains unclear.
Significance of the study
This study is particularly relevant for the TBI population in Northwest Syria, a region where ongoing conflict has severely disrupted the healthcare infrastructure and limited access to advanced neuromonitoring and specialized neurocritical care. By introducing and evaluating a nurse-led, RASS-guided sedation protocol, this study provides context-specific evidence for improving sedation quality, pain management, and overall patient safety in general ICUs with scarce resources. The findings not only address an urgent gap in clinical practice, but also empower nurses, who are often the primary frontline caregivers in such settings, with practical, standardized tools to optimize care. Ultimately, this study will contribute to reducing complications, improving patient outcomes, and enhancing the resilience of critical care services for patients with TBI in one of the most vulnerable healthcare contexts worldwide. This study aimed to evaluate the effects of a nurse-led sedation protocol on sedation quality and care practices for patients with TBI in a resource-limited setting.
METHODS
Design
This study used a randomized controlled trial design. The study was conducted across three general ICUs in Northwest Syria, reflecting a multicenter structure. It followed a single-blind, open-label approach; research assistants responsible for patient assessment and data collection were blinded to group allocation (intervention vs. control), whereas blinding of nurses and patients was not feasible because of the clinical nature of the nursing intervention.
Sample
A consecutive sample of 80 adult patients with TBI was enrolled and randomly allocated into the control and intervention groups (40 patients in each group). The sample size was calculated to achieve 80% power to detect a moderate effect size (d=0.6) at the 5% significance level, resulting in a requirement of 34 participants per group (n=68). The calculation was conducted in consultation with a senior biostatistician, taking into account the expected ICU admission rate and the planned 6-month data-collection period. The assumed effect size was informed by previously published randomized clinical trials evaluating protocolized sedation in intensive care settings [17,19,20], which consistently reported moderate effect sizes (d=0.5–0.8) for key outcomes such as RASS adherence, sedation adequacy, and clinical recovery. This conservative yet realistic estimate ensured sufficient statistical power to detect clinically meaningful differences between the intervention and control groups, and allowed for an anticipated dropout rate of 10%, resulting in a total enrollment of 80 participants.
Randomization was performed using block randomization (block size=10) generated in Microsoft Excel, creating eight blocks of 10 participants each. The randomization sequence was prepared by an independent researcher, and allocation concealment was ensured using opaque, sealed envelopes, which were opened only after confirming participant eligibility and collecting the baseline data. Eligible participants were adults aged 18–60 years with TBI who required endotracheal intubation within 24 hours of ICU admission, had a Glasgow Coma Scale (GCS) score of 7–12, an RASS score greater than −4, and an Acute Physiology and Chronic Health Evaluation II (APACHE II) score between 10 and 19. Patients were excluded if they had a GCS score <6, pre-existing neurological disorders or substance use, planned early extubation, underwent surgery during enrollment, or required continuous sedative infusion.
Tools
Four tools were used by the researchers in the present study.
Tool 1: patient data-collection tool
This tool, which was developed by the researchers after a comprehensive review of related literature [20,21], is a patient data-collection form that includes demographic information (patient code, sex, age, medical diagnosis, and admission and discharge dates) and relevant clinical data (diagnosis at admission, history of chronic diseases, cause of injury, indication for sedation, and baseline APACHE II, RASS, and Behavioral Pain Scale [BPS] scores).
Tool 2: multi-clinical scales tool
This tool consisted of four parts. Part I was the RASS, a validated 10-point scale assessing sedation depth (+4 to −5). Part II was the BPS, which evaluates facial expressions, upper limb movements, and ventilator compliance, with scores ranging from 3 (no pain) to 12 (severe pain) [22]. Part III was the GCS, revised in 2005, with scores ranging from 3 (deep coma) to 15 (fully alert) [23]. Part IV was the APACHE II, which has been validated for predicting ICU mortality across settings [24].
Tool 3: pharmacological and non-pharmacological interventions checklist
This checklist consisted of two parts. Part I addressed non-pharmacological measures, including psychological support, family communication, physiotherapy, patient positioning, noise and light reduction, adequate sleep, temperature regulation, airway suctioning, reducing pressure from connections, and the use or removal of physical restraints. Part II covered pharmacological management, detailing the use of sedatives such as midazolam, propofol, dexmedetomidine, thiopental, fentanyl, and morphine along with their respective frequencies and dosages.
Tool 4: TBI nurse-led sedation protocol
The nurse-led, RASS-guided sedation protocol was specifically developed and tailored for this study on the basis of an extensive review of international sedation guidelines [9,20,21], adaptation to local ICU resources, and validation by a panel of critical care experts to ensure clinical feasibility and applicability. The protocol included regular RASS assessments, titration of sedative infusions to maintain target sedation levels, and prioritization of non-pharmacological interventions to optimize patient comfort and minimize unnecessary sedative exposure (Fig. 1).
Data Collection
Preparatory phase
The study was conducted in three general ICUs (25 beds) in Northwest Syria. Data were collected over 6 months (February–July 2025). A pilot study involving nine patients was conducted to evaluate the clarity, applicability, feasibility, and completion time of the study tools; these patients were excluded from the main study analysis. Content validity was confirmed by seven experts from nursing and critical care, and this exercise led to tool modifications. Reliability testing of Tool I showed good internal consistency (Cronbach’s alpha=0.86). Separately, research assistants (age, 26–38 years; ≥3 years of ICU experience) received 4 hours of training on TBI sedation and RASS, and applied the protocol to five patients to ensure substantial inter-rater reliability with the principal researcher (Cohen’s kappa=0.77; 95% CI, 0.62–0.92).
Assessment phase
On admission, the study participants underwent demographic assessments and measurement of clinical scores (RASS, BPS, GCS, and APACHE II). The control group received routine ICU care, which was non-protocolized and involved intermittent vital sign monitoring, sedative administration according to physician orders, and subjective nurse judgment; the assessment frequency in this group was generally non-standardized. The intervention group received a protocolized sedation regimen. Sedation and pain were monitored at 2-hour intervals, and all interventions were documented and supervised by ICU physicians.
Implementation phase
Non-pharmacological interventions were systematically implemented and documented. These included psychological support, family communication, patient repositioning, airway suctioning, noise and light reduction, adequate sleep promotion, physiotherapy, temperature regulation, management of pressure from medical connections, and application or removal of physical restraints. All interventions implemented for each patient in both the intervention and control groups were recorded.
The nursing sedation protocol (Fig. 1) targeted RASS scores of −2 to +1: no action was taken if the scores were within this range; sedation was reduced if the score was less than −2 without elevated ICP or seizures; and pain correction or non-pharmacological measures were implemented if the score was greater than +1. Assessments were performed every 2 hours, and the protocol was continued throughout the mechanical ventilation period under ICU supervision.
Statistical analysis
Data were reviewed and prepared for computer entry, coded, analyzed, and tabulated using a computer program IBM SPSS version 26 (IBM Corp.). Descriptive analyses were performed using frequencies, percentages, means and standard deviations (for normally distributed continuous variables) and medians and interquartile ranges (for non-normally distributed continuous and ordinal variables). The normality of continuous variables was assessed using the Shapiro-Wilk test. The chi-square test (or Fisher’s exact test, when appropriate) was used for categorical variables. An independent-sample t-test was applied for normally distributed continuous variables, while the non-parametric Mann-Whitney U-test was applied to compare mean values between the study and control groups for non-normally distributed continuous variables (e.g., APACHE II score) and ordinal variables (e.g., RASS and admission GCS scores). To account for repeated measures and within-subject clustering of RASS scores over time, a linear mixed model was employed. The critical value of P was considered statistically significant when it was less than 0.05. Cronbach’s alpha was measured to test the reliability of the tool. Missing values were addressed using list-wise deletion, with analyses performed on a complete-case basis to avoid bias introduced by incomplete data.
RESULTS
Participant flow
Fig. 2 shows that of 128 patients screened, 48 were excluded. Exclusions in phase 1 (n=33) included seven patients who refused consent and 26 patients who did not meet the inclusion criteria (e.g., GCS score <6, pre-existing neurological disorders, or APACHE II scores outside 10–19). Exclusions in phase 2 (n=15, post-eligibility, pre-randomization) included four patients who underwent surgery during the enrollment window and 11 patients who were already deeply sedated, preventing accurate baseline RASS assessment. The final 80 patients were randomized equally into intervention and control groups, with all completing the study
Baseline characteristics
Table 1 shows the baseline characteristics of the participants. Continuous variables with non-normal or ordinal distributions (admission GCS score, APACHE II score, and baseline RASS score) were presented as median (interquartile range). The groups showed no statistically significant differences in age (P=0.132), sex distribution (P=0.284), admission GCS score (P=0.089), APACHE II score (P=0.895), baseline RASS score (P=0.540), and cause of injury (P=0.110). Similarly, the groups showed no significant differences in the indications for sedation, including the control of ICP (P=0.112), reduction of agitation (P=0.189), pain control (P=0.310), tolerance to mechanical ventilation (P=0.152), procedural sedation (P=0.654), seizure management (P=0.531), and promotion of sleep (P=0.314).
Sedation and pain quality
Table 2 shows the results of the linear mixed model analysis examining the changes in the RASS scores over time between the intervention and control groups. The model demonstrated a statistically significant main effect of group and a significant group-by-time interaction (P<0.001 for both), indicating that the trajectory of sedation levels differed significantly between groups. Specifically, in comparison with the control group, the intervention group showed a significantly different rate of change in RASS scores across the monitoring period, consistent with the maintenance of a more desirable sedation target.
Fig. 3 illustrates that the intervention group spent a significantly higher proportion of time (61.6%) in the target sedation range (RASS score, –2 to +1), while the corresponding value for the control group was 30.1%. Conversely, episodes of oversedation (RASS score <–2) were more frequent in the control group than in the intervention group (27.8% vs. 16.4%). Similarly, undersedation (RASS score >+1) occurred more often in the control group than in the intervention group (42.1% vs. 22.0%).
Fig. 4 shows the distribution of the pain levels based on the BPS score in the two groups. The intervention group reported no pain (BPS score ≤3) in 75.5% of the cases, while the corresponding value for the control group was only 24.5%. Similarly, slight pain (BPS score, 4−6) was reported by 64.7% and 35.3% of the patients in the intervention and control groups, respectively. Conversely, moderate pain (BPS score, 7−9) was more frequent in the control group (60.3%) than in the intervention group (39.7%). Episodes of extreme pain (BPS score, 10−12) were also more common in the control group than in the intervention group (67.9% vs. 32.1%). The average BPS score was significantly lower in the intervention group (5.51±2.14) than in the control group (7.88±2.05, P<0.001).
Non-pharmacological interventions and sedative use
Table 3 demonstrates that the intervention group received non-pharmacological interventions more frequently than the control group during both the first 5 days of observation (P<0.001) and the subsequent 5 days (P<0.001) (Table 2). These interventions included psychological support, family contact, repositioning, suctioning, environmental noise/light reduction, pressure relief, sleep promotion, physiotherapy, and restraint management. Table 4 shows that the total duration of sedative infusion was significantly lower in the intervention group (31.93±5.82 hours) than in the control group (37.63±8.40 hours; t=3.53, P=0.001).
DISCUSSION
This randomized controlled trial investigated the influence of a nurse-led sedation care protocol guided by the RASS on sedation quality, pain control, non-pharmacological care practices, and sedative exposure in patients with TBI in a conflict-affected, resource-limited setting. The findings indicated that nurse-led sedation significantly improved the proportion of time patients spent within the target sedation range, enhanced pain management, increased the use of comfort-oriented nursing interventions, and reduced the overall duration of sedative infusion. Collectively, these findings highlight the feasibility and clinical value of empowering nurses to proactively manage sedation in settings where human and material resources are constrained.
At baseline, the intervention and control groups were comparable in terms of demographics, injury severity, and sedation indicators, minimizing confounding factors and supporting valid outcome assessments. Achieving such a balance was challenging in conflict-affected Northwest Syria, where delayed or inadequate prehospital care increases the variability in injury severity and ICU management complexity. The mean age of the patients was in the third decade of life, which is consistent with the fact that TBI disproportionately affects young adults [25]. According to Rosyidi et al. [26], TBI is a major cause of mortality and morbidity in patients aged 18 to 45 years. The study also had a predominance of male patients, consistent with the global and regional data on TBI incidence. Baseline GCS scores in both groups indicated moderate brain injury, whereas APACHE II scores reflected moderate severity of illness.
Regarding the causes of injury, both groups exhibited a mix of road traffic accidents, falls, and war-related injuries, with no significant differences in distribution. This heterogeneity mirrors the complex trauma epidemiology in conflict-affected regions such as Northwest Syria, where civilian injuries arise from both conventional trauma mechanisms and combat-related events [13,27]. This heterogeneity adds external validity to the findings, since the effectiveness of the protocol was demonstrated across diverse injury mechanisms. Similarly, indications for sedation, including ICP control, agitation, pain, ventilator tolerance, procedural needs, seizure management, and sleep promotion, were balanced between the groups. This similarity suggests that the subsequent differences in sedation quality or outcomes were likely due to the intervention.
In comparison with the control group, the intervention group showed a significantly greater proportion of the duration within optimal sedation levels (RASS –2 to +1) and experienced fewer episodes of both over- and undersedation. Thus, structured, nurse-driven protocols can reduce variability in sedation practices and ensure safer titration of sedatives. These findings are consistent with those of previous studies on TBI populations [16]. Reducing both over- and undersedation is especially critical in TBI, since oversedation may mask neurological deterioration, while undersedation can trigger agitation spikes [11].
The superior sedation control observed in the intervention group can be attributed to the implementation of a structured, nurse-led protocol that emphasized continuous bedside assessment and empowered nurses with real-time decision-making authority. This approach enabled prompt adjustments to sedation levels on the basis of standardized tools (RASS and BPS), ensuring that patients remained within the targeted sedation range more consistently. In contrast, the control group followed conventional physician-directed practices, wherein the absence of a structured and mandatory sedation management framework led to inconsistent practices among nurses and reliance on subjective judgment. Such variability often resulted in under- or oversedation. The integration of a clear, actionable protocol not only enhanced the accuracy and timeliness of sedation decisions, but also reinforced nurses’ confidence, accountability, and adherence to evidence-based standards. These factors collectively explain why more effective sedation control was achieved in the intervention group than in the control group.
Patients assigned to the intervention group spent a greater proportion of time with BPS scores ≤6, indicating no or slight pain, and had significantly lower mean pain scores overall. This improvement is consistent with that reported by Wojnar Gruszka et al. [28], who demonstrated that systematic pain assessment in non-communicative ICU patients improved analgesia adequacy. The higher pain levels observed in the control group could be attributed to several factors related to the nature of routine care. One major aspect concerns the nursing workforce, which suffers from a notable shortage of staff due to workload demands. This imbalance often leads to overreliance on traditional manual observation methods, such as monitoring vital signs, instead of employing standardized pain assessment tools. This practice introduces variability in subjective estimations and reduces the accuracy of pain evaluation, particularly among patients who are unable to self-report. Moreover, the demanding ICU environment, characterized by high workloads and competing priorities, often pushes pain management to a lower priority than urgent physiological needs such as maintaining the airway and hemodynamic stability.
The emphasis of the interventional protocol on addressing pain before escalating sedative therapy may explain the observed analgesic benefits. This approach was consistent with SCCM recommendations, which state that pain management should precede the administration of any sedative agent [9]. By integrating pain assessment into sedation decisions, the protocol promoted a more holistic, patient-centered approach. According to the SCCM guidelines for critically ill adult patients who cannot self-report pain, but whose behaviors can be observed, the BPS demonstrates the highest validity and reliability for assessing pain in intubated patients. Conventional vital signs, including heart rate, blood pressure, respiratory rate, and oxygen saturation, are not considered reliable indicators of pain in this population and should only serve as preliminary cues to prompt further evaluation using validated pain assessment tools such as the BPS or other pain scales [9].
In contrast, Waydhas et al. [29] reported that the BPS has limited reliability for pain evaluation in awake, nonverbal patients without delirium. This suggests that assessment alone is insufficient without an actionable protocol, which is a gap that our intervention addressed. This may be due to differences in patient populations or variations in analgesic administration practices. In the context of a war-affected, resource-constrained ICU, maintaining consistent pain assessment and timely management is particularly challenging yet essential for improving patient outcomes and comfort.
The intervention group received more frequent non-pharmacological actions, such as psychological support, family contact, noise/light reduction, and physiotherapy. These measures are integral to the SCCM guidelines. Integrating non-pharmacological strategies enhances patient comfort and reduces agitation, thereby complementing pharmacological sedation [20,30]. However, some reports have shown an inconsistent implementation of these interventions, often due to staffing shortages or high patient-to-nurse ratios. In the current study, the increased application of these interventions underscored the potential of protocols to improve care even under extreme constraints.
Kayambankadzanja et al. [31] reported that anxiety and agitation are frequently observed in patients with TBI and should be mitigated through consistent patient communication, provision of psychosocial support, presence of family members or caregivers, maintaining a quiet environment, facilitating adequate sleep, using restraints to prevent self-extubation and medical device removal, avoiding falls, and protecting staff from combative patients. Non-pharmacological measures can be safe, inexpensive, and effective in managing sleep quality and reducing pain and delirium in ICU patients [32-34]. Overall, the results highlight that integrating structured non-pharmacological interventions within a nurse-led protocol can not only optimize sedation practices, but also promote a more holistic and humane approach to critical care.
The total duration of sedative infusion was significantly lower in the intervention group, demonstrating that nurse-led protocols can reduce sedative exposure. This reduction in sedative exposure may reflect the more accurate titration and better patient monitoring achieved through the nurse-led protocol. Other studies have reported similar reductions in sedative consumption using structured sedation protocols [20], highlighting both the safety and resource efficiency of such protocolized approaches. However, some studies found no reduction in drug use [21], which may reflect differences in protocol adherence or ICU practice culture.
Nevertheless, while lower sedative exposure can enhance patient outcomes, excessive dose reduction without adequate monitoring may increase the risk of agitation or self-extubation. Therefore, the observed improvement suggests that the balance achieved through the structured nurse-led assessment effectively maintained optimal sedation while minimizing harm. These findings reinforce the importance of empowering nurses to adjust sedation within defined safety limits supported by evidence-based protocols. In resource-limited ICUs, reducing sedative consumption is of practical importance for conserving scarce medications and minimizing potential adverse effects.
While the RASS-guided protocol followed established international guidelines, its adaptation and evaluation within the resource-limited conflict-affected ICU setting in Northwest Syria was the novel aspect of this study. The collected data indicated that the protocol primarily enhanced sedation quality, improved pain control, promoted nursing-led non-pharmacological care, and reduced sedative exposure. Although mortality, length of stay, and delirium were not directly measured, reductions in over- and undersedation served as validated intermediate markers of patient safety by mitigating risks such as aspiration, prolonged ventilation, self-extubation, and secondary brain injury. These findings support the need for improvements in sedation management and indirectly contribute to safer patient care.
The generalizability of this protocol to other low-resource or conflict-affected ICU settings is promising. The minimal requirements include simple bedside tools (RASS, BPS), a brief focused 4-hour nurse training session, and a structured, actionable checklist guiding sedation and non-pharmacological interventions. However, the 10-day duration of this study limited the evaluation of long-term outcomes. Future studies should assess patient-centered outcomes, such as the duration of mechanical ventilation, incidence of delirium, ICU and hospital lengths of stay, and mortality, to provide comprehensive evidence of safety, analgesic quality, and resource optimization. The variable ventilation durations required restructuring of the SPSS data. Bias was minimized through randomization, standardized regimens, APACHE II matching, and blinded research assistants.
This study demonstrated that a nurse-led, RASS-guided sedation protocol could enhance sedation quality, improve pain control, promote nursing-led non-pharmacological care, and reduce sedative exposure in mechanically ventilated patients with TBI in a resource-limited, conflict-affected ICU context. This protocol can be integrated into daily practice with minimal equipment, relying on clinical scales and standardized checklists, and the sedative-sparing effect is particularly advantageous in settings with unstable supply chains.
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