Abstract
Objective
Intestinal transplantation (ITx) is a definitive therapy for patients with intestinal failure. However, postoperative respiratory care in such patients remains a clinical challenge. In this study, we investigated the factors affecting the duration of mechanical ventilation in patients who underwent ITx.
Methods
In this observational study, eight patients who underwent ITx between 2007 and 2013 were studied. They were divided into two groups, with Group E including three patients who could be successfully extubated within 72 hours and Group V including the remaining five, who could not be extubated. The differences in demographical and clinical data between the two groups were evaluated.
Results
The surgery success rate, patient survival rate, and graft survival rate were 100%, 88%, and 75%, respectively. Compared with Group E, postoperative bleeding was significantly higher in Group V (700 ± 420.7 mL vs. 50.0 ± 2.0 mL, p = 0.021). In addition, postoperative respiratory complications including pleural effusion and pneumonia (p = 0.017 and p = 0.0714, respectively) were prone to occur in Group V. Other variables including demographic parameters and clinical data showed no significant differences between the two groups. It was not unexpected that the duration of ventilator use and the length of intensive care unit stay were significantly shorter in Group E.
Conclusion
Postoperative blood loss and postoperative respiratory complications might be the factors responsible for delayed extubation in ITx patients. Because the study had few examinees, further studies with a larger population are needed to verify these issues.
Keywords
airway extubation; graft rejection: acute; organ transplantation: intestine; respiration, artificial: mechanical ventilation; tacrolimus;
1. Introduction
Intestinal transplantation (ITx) is accepted as a standard treatment for the patients of intestinal failure with life-threatening parenteral nutrition-related complications.1 Nevertheless, the postoperative respiratory care for these patients appears to be a greater challenge to medical professionals. Compared with other organ transplants, complications including acute cellular rejection (ACR), infection, graft-versus-host disease, and post-transplant lymphoproliferative disease are found to be more frequent in ITx patients. Of note, ACR and infection are the major complications leading to mortality. With the advances of immunosuppressive therapies, improvements in patient and graft survival after ITx are anticipated.1, 2, 3, 4, 5
The ventilatory management is difficult for the patients subjected to ITx perioperatively. Preoperative care includes maintaining adequate organ perfusion, minimizing ventilator induced lung injury, optimizing nutritional support, and preventing excessive edema. Postoperative care may focus on maintaining adequate oxygenation, using lung protective ventilation strategies such as low tidal volumes, peak plateau pressures, and assessing diaphragmatic function if difficulty of weaning is found. Patients may require tracheostomy if and when prolonged ventilatory support is needed, although this is not common in children.6, 7
Early extubation in patients subjected to major and complex surgery is supported by the evidence that early extubation is safe and economical, and reduction of postoperative mechanical ventilation may have clinical and organizational advantages.8 However, ITx is the most difficult organ transplantation and the duration of mechanical ventilation is the longest when compared with other organ transplantations. The optimal timing to remove the endotracheal tube in ITx patients remains unclear. Some patients of ITx transplants can be extubated within 72 hours; however, prolonged mechanical ventilation may be required in certain patients due to unusual conditions.9
The factors affecting extubation in the patients subjected to ITx remain unknown. The first successful ITx was performed in 2007 in Taiwan. To our knowledge, ITx has been done successfully in only eight patients in Taiwan. In this study, we explored the factors that might affect the duration of mechanical ventilation in ITx patients.
2. Methods
This was a prospective, observational study of eight patients who underwent ITx between 2007 and 2013 at the Far Eastern Memorial Hospital (FEMH). The Department of Health, Executive Yuan, Taiwan and the Institutional Review Board and Ethics Committee of the FEMH approved the study. Isolated ITx was performed in six children (75%) and two adults (25%) including one male and seven females with a median age of 13 years (range, 2–64 years). The mean weight of the patients at transplantation was 29.2 ± 12.0 kg (range, 11.0–46.0 kg) and mean waiting time was 366.4 ± 415.2 days. The underlying causes of the patients who underwent ITx included short bowel syndrome in three patients (38%) and Hirshsprung's disease in two patients (25%). The major indications were repeated catheter-related sepsis in all patients, ischemic bowel and peritonitis in two patients (25%), and liver function impairment in three patients (38%). All grafts were procured from cadaveric donors.
All patients were under endotracheal general anesthesia for the surgery. The mean operation time was 8.4 ± 3.5 hours. After surgery, patients were transferred to the intensive care unit (ICU) and weaned from the ventilator if and when the situation met with clinical criteria. The weaning protocol was as follows: patient awake; clinical evidence of neuromuscular reversal as evidenced by positive cough and gag reflex; pH > 7.35; normocapnia (end tidal CO2, 30–40 mmHg; partial pressure of arterial CO2, <50 mmHg); respiratory rate < 25 breaths/minute; tidal volume > 5 mL/kg; minute ventilation < 15 L/min; and partial pressure of arterial O2 > 80 mmHg (oxygen saturation > 95% with fraction of inspired oxygen ≤ 0.4). Patients should be warm, well perfused, hemodynamically stable, and without ongoing blood loss or requirement for inotropic agents. The immunosuppressive regimen included thymoglobulin for induction therapy, and tacrolimus and steroids for maintenance therapy. The blood level of tacrolimus was kept in the range of 15–20 ng/mL. Standard antibiotic prophylaxis and prophylactic antifungal agents were given. Immunosurveillance of the intestine was done endoscopically with biopsy twice/week. Patients were extubated if permissible clinically. After extubation, supplemental oxygen was given by facemask and thoracic physical therapy was enhanced. Arterial blood gas analysis was performed to guide oxygen therapy. Chest radiograph was performed to check for chest problems. The patients were divided into two groups based on whether or not extubation was within the first 72 hours after surgery.6, 9, 10Three patients were successfully extubated within 72 hours after ITx (Group E) and five were not (Group V).
The data are expressed as mean ± standard deviation, median, or percentile. Comparison between two independent groups was done using Mann–Whitney U test and Chi-square test with Fisher exact test when appropriate. Statistical significance was defined as p < 0.05 (two-tailed). Statistical analysis was performed using SPSS (version 16; SPSS Inc., Chicago, IL, USA).
3. Results
The surgery success rate, patient survival rate, and graft survival rate were 100%, 88%, and 75%, respectively. The mean ICU stay was 23.0 ± 16.5 days and mean hospital stay was 49.7 ± 22.9 days. ACR occurred in four patients (50% of 8 patients). Three mild ACR and two severe ACR were diagnosed within the first month after ITx. One patient's graft was removed due to ACR. Definitive abdominal closure was achieved in all cases without the aid of prosthetic material. Six patients terminated total parenteral nutrition 24 days after ITx and demonstrated significant weight gain.
Three patients (38%) were successfully extubated within 72 hours after surgery (Group E) and five patients (62%) were not (Group V). Comparisons of the demographic data and general clinical data between the two groups are shown in Table 1. No significant differences in the variables between the two groups were found except that the length of hospital stay was found to be longer in Group V (p = 0.018).
Comparisons of the data related to ITx are shown in Table 2. There were no significant differences in the variables between the two groups except that a greater amount of postoperative bleeding was found in Group V (p = 0.021). Comparisons of the data related to the use of ventilator support between the two groups are shown in Table 3. It was not unexpected that the duration of ventilator use was longer in Group V (p = 0.023), associated with more CXR taken (p = 0.024), and arterial blood analysis carried out (p = 0.025).
Comparisons of the data on ICU stay and related complications between the two groups are summarized in Table 4. Significantly longer ICU stay (p = 0.021) was found in Group V and higher mean blood level of tacrolimus was found in Group E (p = 0.025). Occurrence of pleural effusion was more common in group V (p = 0.018) and pneumonia was prone to develop in Group V (p = 0.074). Other variables showed no significant differences between the two groups.
4. Discussion
A previous study indicates that early extubation could reduce the risk of ventilator-associated pneumonia, shorten the length of ICU stay, and improve the utilization of resource.8 Most patients could be extubated within the first 24 hours after organ transplant surgery except for those who underwent ITx. ITx patients usually require endotracheal intubation for several days, although early extubation may be found in certain patients. In this study, five patients (62%) remained intubated for more than 72 hours, and only one adult patient was extubated within the first 24 hours after ITx. Most patients required ventilatory support for at least 48 hours in the early postoperative period, because they were susceptible to significant fluid shifts. Adequate management of fluid and electrolytes is crucial to avoid pulmonary edema or renal failure. ACR, graft malfunction, abdominal distension, intra-abdominal bleeding, and inability to close the abdominal wall are circumstances that hinder early extubation.9
In agreement with a previous report,9 our results indicated that postoperative bleeding might be the factor responsible for delayed ventilatory support (Table 2). However, some other factors highly suggestive of being responsible for delayed extubation in ITx patients were not supported by our results. Of note, all patients in Group V were pediatric, and pediatric patients were reported to significantly subject ITx patients to respiratory infections and more severe multisystem impairments which could delay extubation.2, 6, 7Limited cases studied may explain the discrepancy between ours and previous studies. Furthermore, pool analysis of the pediatric and adult patients is not without flaw because the underlying diseases leading to intestine failure and the impact on ITx on pathophysiological status between pediatric and adult patients can be different. Further studies with a larger population are needed to verify these issues.
Respiratory complications including pleural effusions and ventilator-associated pneumonia were found more often in the Group V patients (Table 4). The respiratory complications might compromise the respiratory function and hinder early extubation of the patients subjected to ITx. However, the causal effect of these complications on delayed extubation could not be confirmed because delayed extubation could result in these complications. As a consequence, the timing of occurrence and severity of these complications related to ITx are of considerable importance in differentiating whether these complications are the causes or complications of delayed extubation.
There are limitations in this study. First, a small number of cases were studied, therefore, a solid conclusion cannot be drawn from the results, which should be interpreted with caution. Second, pediatric and adult patients were pooled for analysis. The results should also be interpreted with caution because pediatric and adult patients could be considerably different in terms of pathophysiological response to ITx. Third, the indications of ITx were diverse. The heterogeneity of the underlying diseases may make the comparisons difficult and to draw a conclusion from these results could be challenging. However, the results of the present study might be of clinical relevance. Postoperative bleeding may be one of the important factors responsible for delayed extubation. In addition, the occurrence of respiratory complications including pleural effusion and pneumonia after ITx may compromise respiratory function of the patients and hinder early extubation. Furthermore, these domestic data may be of considerable value and encouragement to the domestic physicians involved in ITx.
In conclusion, our results indicated that postoperative bleeding and/or respiratory complications might delay early extubation in ITx patients. Because the case number evaluated is limited in this study, further studies with a larger population are needed to verify these issues.
Acknowledgments
The authors thank Dr Fang-Ming Hung, Dr Chung-Wei Chen, and the intestinal transplant team at FEMH for their excellent care of these challenging patients and for pushing forward the frontiers of ITx in Taiwan.