Comprehensive oral care protocol reduces oral complications in liver transplant recipients: A retrospective cohort study

Abstract

BACKGROUND

Liver transplant recipients are at high risk for oral complications due to obligatory immunosuppression and critical illness.

AIM

To evaluate the impact of a comprehensive oral care protocol on oral health outcomes in postoperative nursing for liver transplant.

METHODS

We conducted a retrospective cohort study of 277 liver transplant recipients. Patients received either a comprehensive oral care intervention (n = 131), which included systematic risk assessment with the Oral Assessment Guide, hydration support, family engagement, and targeted therapies, or routine oral care (n = 146). The primary outcome was the incidence of oral complications.

RESULTS

The comprehensive care group experienced a significantly lower incidence of oral complications compared to the routine care group (5.34% vs 13.70%, P = 0.019). Complications emerged later (postoperative day 6 vs postoperative day 3) and accumulated more slowly in the intervention group. Furthermore, patients receiving comprehensive care maintained significantly better and more stable Oral Assessment Guide scores throughout their intensive care unit stay, with a median score of 7 from day 5 onwards, vs a median score of 9 in the routine care group (P < 0.05).

CONCLUSION

A nurse-led, comprehensive, protocol-driven oral care strategy significantly improves oral health outcomes by reducing and delaying complications in critically ill liver transplant recipients.

Key Words: Liver transplantation; Oral care; Oral complications; Intensive care units; Immunosuppression

Core Tip: This retrospective cohort study of 277 liver transplant recipients shows that a nurse-led comprehensive oral care protocol - including Oral Assessment Guide-based risk stratification, hydration support, family engagement, and targeted therapies - significantly reduces the incidence of oral complications, delays the onset of oral complications, and maintains better oral health vs routine care.

INTRODUCTION

Liver transplantation is the most effective treatment for end-stage liver disease[1]. However, the success of this procedure is largely dependent on the continuous use of immunosuppressive agents in the perioperative period to prevent allograft rejection[2]. The initiation of immunosuppression, typically including calcineurin inhibitors, antiproliferative agents, and corticosteroids, begins immediately post-reperfusion and is maintained for life[3,4]. While lifesaving, this iatrogenic immunosuppression renders patients profoundly immunocompromised. This state, combined with surgical trauma, side effects of adjunct medications, and environmental factors in the intensive care unit (ICU), significantly increases the risk of oral complications[5]. Three primary factors contribute to the prevalence of oral complications in this patient population. First, immunosuppressants and antibiotics are associated with the induction of oral ulcers and candidiasis, while diuretics and sedatives frequently precipitate medication-related xerostomia[6]. Second, interventions such as orotracheal intubation and high-flow oxygen therapy compromise oral mucosal integrity and disrupt the physiological humidification microenvironment, thereby predisposing patients to dryness, ulceration, and secondary infections[7]. Third, A compromised immune system disrupts the homeostasis of the oral microbiome, facilitating the over-proliferation of opportunistic pathogens and subsequent development of infectious stomatitis. In addition, it is reported that oral problem can affect a large proportion of the patients awaiting liver transplantation[8,9], which increases the risk of postoperative oral complications.

These oral complications not only cause significant discomfort, impair nutritional intake, and reduce quality of life but also represent potential portals for systemic infection. In immunocompromised hosts, localized oral infections can rapidly disseminate, leading to bacteremia or fungemia, which may prolong hospital stays, increase healthcare costs, and even jeopardize graft and patient survival. Critical care nurses, as primary caregivers, play a pivotal role in the prevention, early detection, and management of these complications. Toothbrushes, foam swabs, and moisturizers are the most commonly used tools for oral care in the ICU[10,11]. An enhanced oral care strategy, consisting of toothbrush, toothpaste, mouthwash, and moisturizers and performed twice daily, significantly reduced the incidence of oral health dysfunction in the ICU[12]. Therefore, oral care intervention led by the critical care team is essential to mitigate the adverse oral events of patients in ICU. In our department, a comprehensive oral care protocol has been applied to post-transplant care. This study aimed to retrospectively evaluate the efficacy of this comprehensive oral care protocol on the oral health outcomes of liver transplant recipients.

MATERIALS AND METHODS

Study design and setting

This was a single-center, retrospective cohort study conducted in the ICU of Shulan (Hangzhou) Hospital. The study was designed to compare the outcomes of patients receiving a comprehensive oral care intervention vs those receiving routine oral care. Perioperative treatment strategies were in line with the guidelines[3,13,14].

Study population

The electronic medical records of all patients admitted to the ICU following liver transplantation between August 1, 2023, and August 31, 2025, were screened for eligibility.

The inclusion criteria included: Adult patients (aged ≥ 18 years) underwent first-time allogeneic liver transplantation. The exclusion criteria were as follows: Pre-existing severe oral diseases or maxillofacial tumors prior to transplantation; patients requiring emergency re-transplantation; patients with severely incomplete clinical data; patients who died or withdrew from active treatment within 72 hours post-transplantation.

Group allocation

Eligible patients were divided into two groups based on the oral care protocol they received and the time period of their ICU stay: Comprehensive care group: Patients admitted between August 2024 and August 2025, who received the standardized comprehensive oral care intervention. Routine care group: Patients admitted between August 2023 and July 2024, who received routine oral care.

Oral care interventions

Routine oral care included: (1) Tooth brushing with a soft-bristled brush twice daily (morning and evening); (2) Routine use of chlorhexidine mouthwash for rinsing or irrigation every 8 hours; and (3) For patients who developed oral complications, targeted treatments such as nystatin glycerin, sodium bicarbonate mouthwash, or lidocaine-containing ulcer patches were applied based on the oral condition. The comprehensive oral care intervention, executed by the critical care nursing team, consisted of the three core components.

Comprehensive initial assessment and risk stratification: A baseline assessment using the standardized Oral Assessment Guide (OAG)[15] was performed within 2 hours of ICU admission, followed by reassessments every 24 hours. The OAG scale we applied here included assessment of the lips, tongue, mouth mucosa, gingiva and saliva. Each item is scored from 1 to 3, with a higher score indicating a worse condition. Patients were stratified into low (OAG score 5-6), medium (OAG score 7-9), or high risk (OAG score ≥ 10) to guide the frequency and intensity of subsequent care.

Basic care and hydration: (1) Dry mouth was assessed every 4 hours using a thirst numerical rating scale or an oral mucosa moisture scale; (2) Promotion of self-management in conscious patients: Safety for oral intake was assessed based on clinical status, fluid balance requirements, consciousness level, airway protection ability, and gastrointestinal function. Conscious patients were educated to actively report dry mouth severity (e.g., using a Numerical Rating Scale and were trained in basic hydration skills (e.g., small sips and rinses, use of spray bottles, lip balm, chewing gum, or oral exercises to stimulate saliva). Health education emphasized the necessity of hydration to enhance compliance; (3) Family involvement: Families were educated using an “ICU Patient Dry Mouth Education Manual” and instructional videos. They were provided with a kit (including bottled water, lip balm, a spray bottle) and could request personalized moisturizing solutions (e.g., with glycerol, mint, borneol, lemon). Families were encouraged to participate in oral care during visits (e.g., moistening lips with cotton swabs, oral spraying) for emotional support; and (4) Dynamic feedback: Patient/family feedback was collected weekly to optimize the intervention.

Targeted interventions: (1) Fungal infection prevention: Medium-risk and high-risk patients routinely received oral probiotic supplements; (2) Fungal infection management: Affected patients received sodium bicarbonate mouthwash every 4 hours and topical nystatin glycerin (as prescribed); (3) Ulcer management: For established ulcers, healing-promoting agents such as recombinant human epidermal growth factor gel or Kangfuxin liquid were applied topically. For severe pain, lidocaine-containing ulcer patches were used; and (4) Management of patients receiving oxygen therapy: For patients on high-flow oxygen therapy, proper function of the humidifier was ensured (aiming for near-airway gas temperature of 36-37 °C), and oral hydration measures were intensified.

Data collection

The following data were extracted from electronic medical records: (1) Baseline characteristics: Age, sex, height, weight, primary liver disease, Model for End-Stage Liver Disease (MELD) score, duration of surgery, intraoperative fluid balance (transfusions, infusions, blood loss, urine output), postoperative fluid balance; and (2) Treatment-related data: Immunosuppressive regimen and duration of invasive mechanical ventilation.

All oral assessments were performed by critical care nurses with ≥ 3 years of clinical experience in transplant ICU nursing, who had completed specialized training in oral health assessment for patients.

Outcome measures

The primary outcome included the incidence of oral complications (ulcers, oral candidiasis, mucositis, xerostomia-related fissures, etc.). The secondary outcomes included changes in OAG scores, ICU length of stay, and mortality in ICU.

Oral complications were defined and diagnosed based on standardized clinical criteria as follows: Oral ulcers: Localized breaks in the oral mucosal epithelium (≥ 3 mm in diameter) with erythematous borders and central ulceration, causing pain or discomfort. Traumatic lesions directly caused by medical devices were excluded. Oral candidiasis: Clinical manifestations including white, curd-like plaques on the oral mucosa (tongue, buccal mucosa, or palate) that are removable with gentle scraping, accompanied by underlying erythema; confirmed by positive potassium hydroxide (KOH) smear or fungal culture when clinically uncertain. Oral mucositis: Inflammation of the oral mucosa characterized by erythema, edema, or ulceration (without evidence of fungal or bacterial infection), graded according to the OAG mucosal assessment item (score ≥ 2, indicating moderate to severe inflammation). Xerostomia-related fissures: Linear cracks (≥ 2 mm in length) on the lips or oral mucosa, directly attributed to inadequate oral hydration (confirmed by oral mucosa moisture scale score < 25% or thirst numerical rating scale score ≥ 4) and excluding other etiologies (e.g., trauma, infection).

Statistical analysis

Statistical analyses were performed using SPSS software (version 26.0). Continuous variables were presented as mean ± SD or median (interquartile range) and compared using the Student’s t-test or Mann-Whitney U test. Categorical variables were expressed as n (%) and compared using the χ² test or Fisher’s exact test. Multivariate logistic regression analysis was employed to adjust for potential confounding factors and to identify whether the comprehensive oral care intervention was an independent protective factor against oral complications. A two-sided P < 0.05 was considered statistically significant.

The OAG scores were compared within 12 postoperative days according to the ICU stay duration of 75% patients. Due to some patients discharged from ICU, the sample size of each group used for OAG comparisons gradually decreased from day 5 to day 12.

Ethical considerations

This retrospective study utilized existing medical records without interfering with patient care. This retrospective cohort study was approved by the Research Ethics Committee of Shulan (Hangzhou) Hospital (Approval No. KY2025137). A waiver of informed consent was requested due to the retrospective nature. All patient data were anonymized and handled confidentially.

RESULTS

Of the 301 patients assessed for eligibility, 14 underwent a second transplant, 5 discharged from ICU within 72 hours due to death or other reasons, 3 had severe oral diseases preoperatively, and 2 underwent an emergency re-transplantation. Therefore, 277 patients were eligible for this study. Figure 1 shows the study flowchart.

Figure 1 Flowchart of this study. ICU: Intensive care unit.

Baseline and perioperative characteristics

The baseline demographic and clinical characteristics of the two groups were well-balanced, as shown in Table 1. There were no statistically significant differences in sex distribution, age, body weight, height, or preoperative MELD score between the two groups (all P > 0.05).

Table 1 Baseline data of the patients, n (%)/mean ± SD/median (interquartile rage).

	Routine care group (n = 146)	Comprehensive care group (n = 131)	P value
Male	122 (83.56)	98 (74.81)	0.072
Age (years)	51.29 ± 10.60	52.47 ± 11.00	0.365
Body weight (kg)	67.67 ± 12.83	65.83 ± 13.32	0.245
Height (cm)	168.96 ± 6.29	167.54 ± 6.97	0.076
MELD score	40 (28.5-40)	40 (19-40)	0.670

MELD: Model for End-Stage Liver Disease.

Comparison of intraoperative data is detailed in Table 2. The duration of surgery, allogeneic and autologous blood transfusion volumes, blood loss were comparable between the groups (all P > 0.05). Furthermore, all patients in both groups were administered with glucocorticoid for intraoperative immunosuppressive induction.

Table 2 Comparison of intraoperative data, mean ± SD/median (interquartile rage)/n (%).

	Routine care group (n = 146)	Comprehensive care group (n = 131)	P value
Surgery duration (hours)	6.36 ± 1.49	6.10 ± 1.22	0.107
Allogeneic blood transfusion (U)	8.5 (5.5-12)	7.5 (4.25-10.75)	0.323
Autologous blood transfusion (mL)	800 (500-1250)	600 (450-1025)	0.386
Plasma transfusion (mL)	1100 (700-1250)	1040 (600-1200)	0.284
Platelets (U)	0 (0-0)	0 (0-0)	0.902
Total infusion (mL)	7950 (6535-9515)	6915 (5860-8445)	0.007
Blood loss (mL)	1500 (1000-2000)	1200 (1000-1500)	0.092
Intraoperative immunosuppressive induction
Glucocorticoid	146 (100)	131 (100)	1.000

Postoperative data are presented in Table 3. The use of basiliximab for postoperative immunosuppressive induction was comparable between the groups (99.32% vs 97.71%, P = 0.539). The maintenance immunosuppressive regimen showed a continued, significantly higher usage of mycophenolate mofetil in the comprehensive care group (77.10% vs 25.34%, P < 0.001), while the use of cyclosporine A (2.74% vs 3.05%, P = 1.000), glucocorticoid (84.93% vs 78.63%, P = 0.173), and tacrolimus FK506 (95.21% vs 95.42%, P = 0.993) were not significantly different. Other postoperative parameters, including the incidence of leukopenia (20.55% vs 18.32%, P = 0.640), duration of mechanical ventilation [17 (12-60.5) vs 16 (13-26.5), P = 0.634], and ICU length of stay [7.9 (5.6-13.5) vs 7.0 (4.8-11.5), P = 0.481], were not significantly different between the two groups.

Table 3 Comparison of postoperative data, n (%)/median (interquartile rage).

	Routine care group (n = 146)	Comprehensive care group (n = 131)	P value
Postoperative immunosuppressive induction
Basiliximab	145 (99.32)	128 (97.71)	0.539
Immunosuppressive maintenance
Cyclosporine A	4 (2.74)	4 (3.05)	1.000
Glucocorticoid	124 (84.93)	103 (78.63)	0.173
Tacrolimus FK506	139 (95.21)	125 (95.42)	0.993
Mycophenolate mofetil	37 (25.34)	101 (77.10)	< 0.001
Postoperative leukopenia	30 (20.55)	24 (18.32)	0.640
Postoperative mechanical ventilation time (hours)	17 (12-60.5)	16 (13-26.5)	0.634
ICU stay (days)	7.9 (5.6-13.5)	7.0 (4.8-11.5)	0.481
OAG score
Day 1	5 (5-6)	5 (5-6)	0.958
Day 2	6 (5-7)	6 (6-6)	0.202
Day 3	6 (6-7)	6 (6-7)	0.008
Day 4	7 (7-8)	7 (7-7)	0.012
Day 5	8 (8-9); n = 142	7 (7-7); n = 117	< 0.001
Day 6	9 (9-10); n = 121	7 (7-7); n = 98	< 0.001
Day 7	9 (9-10); n = 96	7 (7-7); n = 74	< 0.001
Day 8	9 (9-10); n = 83	7 (7-7); n = 66	< 0.001
Day 9	9 (9-10); n = 65	7 (7-7); n = 58	< 0.001
Day 10	9 (9-10); n = 53	7 (7-7); n = 50	< 0.001
Day 11	9 (9-10); n = 47	7 (7-7); n = 42	< 0.001
Day 12	9 (9-10); n = 40	7 (7-7); n = 35	< 0.001
Oral complications	20 (13.70)	7 (5.34)	0.019
Survival rate at ICU discharge	98.63%	99.23%	1.000

Five items of Oral Assessment Guide were included in this study and therefore the scores ranged from 5 to 15. ICU: Intensive care unit; OAG: Oral Assessment Guide.

Oral health outcomes

The primary and secondary outcomes related to oral health demonstrated significant benefits associated with the comprehensive oral care protocol. The incidence of oral complications (including ulcers, oral candidiasis, mucositis, and xerostomia-related fissures) was significantly lower in the comprehensive care group compared to the routine care group (5.34% vs 13.70%, P = 0.019; Table 3). As for the onset of oral complications, the routine care group exhibited its first complications on postoperative day 3, while the comprehensive care group showed no complications until postoperative day 6 (Figure 2). The cumulative incidence in the routine care group demonstrated a continuous and steep increase, particularly during the mid-to-late postoperative period (days 7-9; Figure 2). The comprehensive care group, however, maintained a consistently low incidence rate with a slow and gradual increase throughout the observation period (Figure 2).

Figure 2 Cumulative incidence of oral complications in the routine care group and comprehensive care group.

The trajectory of oral health, as measured by the OAG score, is detailed in Table 3. The median OAG scores were comparable between the two groups on day 1 and day 2 post-transplantation. However, a statistically significant divergence emerged from day 3 onwards. Among patients remaining in the ICU, from day 5 to day 12, the comprehensive care group consistently maintained a median OAG score of 7, indicating a stable, healthier oral status. In contrast, the median OAG score in the routine care group progressively worsened, reaching and maintaining a score of 9 from day 5 onwards, with the differences being highly statistically significant.

To further validate the independent association between the comprehensive oral care intervention and reduced oral complications, we performed a multivariate logistic regression analysis adjusting for potential confounders, including mycophenolate mofetil use, preoperative MELD score, duration of mechanical ventilation, intraoperative total infusion volume, and postoperative leukopenia. The comprehensive oral care intervention remained an independent protective factor against oral complications (adjusted odds ratio = 0.31, 95% confidence interval: 0.12-0.80, P = 0.016). Notably, mycophenolate mofetil use was associated with a trend toward increased risk of oral complications, though this did not reach statistical significance (adjusted odds ratio = 1.87, 95% confidence interval: 0.76-4.58, P = 0.179). Finally, the ICU survival rate was similarly high in both groups (97.71% vs 96.58%, P = 0.839; Table 3).

DISCUSSION

This single-center retrospective cohort study demonstrates that the implementation of a comprehensive oral care protocol significantly improves oral health outcomes in liver transplant recipients during their ICU stay. The key findings reveal that patients receiving the comprehensive intervention experienced a markedly lower incidence of oral complications, a delayed onset of these complications, and consistently better oral health status as reflected by OAG scores, compared to those receiving routine oral care.

These findings suggest that a bundled oral care intervention - incorporating risk stratification, hydration support, family involvement, and targeted topical treatments - may effectively preserve oral mucosal integrity and reduce the incidence of secondary infections in a highly vulnerable population. The stable OAG scores maintained by the comprehensive care group from day 5 onward further support the role of sustained oral care in preventing the deterioration of oral health.

The beneficial effects observed in our study may be attributed to several factors. First, the use of the OAG enabled early identification of high-risk patients and allowed for personalized care intensity, since this is a vital element for oral care plans[16,17]. Second, the emphasis on hydration and active family involvement likely improved adherence and self-management. Third, targeted interventions such as probiotic supplementation and the use of healing-promoting agents may have directly addressed the pathophysiology of mucosal injury and fungal overgrowth[18,19].

However, it is noteworthy that the two groups were not perfectly balanced in all perioperative variables. The use of mycophenolate mofetil was more frequent in the comprehensive care group. It is known that the common side effects of mycophenolate mofetil include leukopenia and oral mucositis, which theoretically increase the risk of oral complications in patients[20]. However, the incidence of oral complications in the comprehensive care group was significantly lower, which indicates the potent effects of our comprehensive oral care.

Our results are consistent with previous studies emphasizing the importance of oral care in critically ill patients. Hua et al[21] and Zhao et al[22] summarized that oral care reduced ventilator-associated pneumonia in mechanically ventilated patients, though it did not influence the mortality and duration of ICU stay. Our study focuses oral complications in liver transplant recipients, a population at high risk for oral complications due to immunosuppression and prolonged ICU stays. The results underscore the importance of a comprehensive oral hygiene care for liver transplant recipients.

This study has several limitations that should be considered when interpreting the results. First, its retrospective and non-randomized design inherently carries risks of selection bias and unmeasured confounding. Although we employed statistical adjustments for key baseline and perioperative variables, residual confounding from factors not captured in the medical records may persist, such as subtle changes in nursing staffing levels, updates to oral care product formulations, or variations in patient education materials. However, given that the comprehensive oral care intervention was the only systematic change in oral health management during the study period, and the consistency of other clinical practices, the impact of such unmeasured factors is likely minimal. Second, the comprehensive oral care was implemented as a bundled intervention. Consequently, it is impossible to discern the individual contribution of each component (e.g., risk stratification, family involvement, or specific topical treatments) to the overall observed benefits. The synergistic effects within the bundle prevent the identification of the most active elements. Third, as a single-center study conducted in a specialized transplant ICU, the generalizability of our findings may be limited. Differences in institutional protocols, nursing expertise, and patient populations could affect the efficacy and feasibility of implementing this protocol elsewhere. In addition, data of assessment consistency were not provided due to the study design. However, according to our work standards, all assessments were performed using a standardized checklist. Assessments were conducted at the same time of day (between 08:00-10:00). In addition, the nursing leaders would conduct a spot check in daily work. We will perform a prospective study to further validate this oral care protocol and then popularize it.

CONCLUSION

This study provides evidence that a nurse-led comprehensive oral care protocol can significantly reduce the incidence and delay the onset of oral complications in liver transplant recipients during their ICU stay. The protocol also contributed to maintaining better oral health status as reflected by OAG scores. These findings support the integration of structured, nurse-led oral care into standard postoperative management for this high-risk population. Further prospective, multicenter studies are warranted to validate these results and to refine the intervention strategies.