Possible case of bortezomib-induced ileus paralytic.

This report describes a case of a patient with active multiple myeloma who was started on bortezomib, cyclophosphamide and dexamethasone and subsequently presented to the emergency department with acute intestinal obstruction one week later. The patient underwent exploratory laparotomy, but no mechanical cause of the obstruction was found. The patient later developed sepsis and eventually died. The possible cause of the intestinal obstruction was attributed to bortezomib, and the paper discusses the potential mechanism of this side effect and its management based on available literature.

Ileus in patients treated with immune checkpoint inhibitors: A retrospective, pharmacovigilance study using Food and Drug Administration Adverse Event Reporting System database.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) have been widely used in cancer treatment; however, some case reports suggested that ICIs treatment might result in ileus. This study aims to comprehensively reveal the relationship between ileus and ICIs treatment in real-world cases from Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). METHODS: Reports from January 1, 2011 to December 31, 2020 were extracted from the FAERS. ICIs-related adverse events in patients were defined as related to use of anti-programmed cell death protein 1 antibodies (PD-1, nivolumab and pembrolizumab), anti-programmed cell death-ligand 1 inhibitors (PD-L1, atezolizumab, durvalumab, avelumab, and cemiplimab), and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, ipilimumab and tremelimumab). ICIs-related ileus cases were identified to characterize their clinical features. Reporting odds ratios (ROR) and information component (IC) were used to assess the relationship between ICIs and ileus. RESULTS: Among the 105 001 cases related to ICIs, 245 were reported with ICI-related ileus. The affected patients were mainly elderly (median age, 64.5 years) and male (58%, n = 143). The median onset for all cases was 36 (range 0-880) days, and no statistical difference was observed between monotherapy and combination therapy (PD-1 or PD-L1 plus CTLA-4) (p = 0.21). Most patients required drug withdrawal treatment (n = 113, 74%) and can achieve a recovered-resolved state (n = 72, 46%). All ICIs were significantly associated with ileus (ROR = 4.27, 95%Cl: 3.75-4.85; IC = 2.04, 95%Cl: 1.79-2.31). Ileus events were most commonly reported in PD-1 treatment (n = 164, ROR = 3.83, 95%Cl: 3.28-4.48; IC = 1.90, 95%Cl: 1.62-2.21). CONCLUSION: This pharmacovigilance database analysis suggested that ICIs are related to ileus. However, combination therapy may not speed up the onset of ileus.

Targin®: An effective opiate analgesia with minimal gastrointestinal side effects-An observational study.

OBJECTIVE: To examine the role of Targin® (oral oxycodone:naloxone combination) in the perioperative setting. DESIGN: A single center prospective observational pilot study at a regional hospital. SETTING: Thirty-eight eligible patients undergoing major general surgical operations were recruited. Thirty-two patients completed the study. INTERVENTIONS: Participants were given Targin twice daily from day 2 post-operatively with twice daily measures of pain scores, gut function, and mobility. MAIN OUTCOME MEASURES: The primary end points were analgesic efficacy and the rate of ileus. Secondary end points were gastrointestinal (GI) recovery and the need for opioid requirement on discharge, at 1 week and 1 month. RESULTS: Average pain score over 5 days at rest was one and on movement was four out of 10. All patients mobilized to a chair by day 3. Twenty-six participants (81.3 percent) experienced nausea at some point during the study, and four participants (12.5 percent) were diagnosed with a post-operative ileus (POI). There was no serious adverse event reported. Only two patients were on opioids at 1-month discharge. This was due to them having Orthopaedic surgery not related to this study.

Vincristine Sulfate Liposome Injection with Bendamustine and Rituximab as First-Line Therapy for B-Cell Lymphomas: A Phase I Study.

BACKGROUND: We conducted an investigator-initiated, phase I trial of vincristine sulfate liposomal injection (VSLI) in combination with bendamustine and rituximab (BR) for indolent B-cell (BCL) or mantle cell lymphoma. METHODS: Participants received 6 cycles of standard BR with VSLI at patient-specific dose determined by the Escalation with Overdose Control (EWOC) model targeting 33% probability of dose-limiting toxicity (DLT). Maximum tolerated dose (MTD) was the primary endpoint; secondary endpoints included rates of adverse events (AEs), overall response rate (ORR), and complete response (CR). Vincristine sulfate liposomal injection is FDA approved for the treatment of patients with recurrent Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL). RESULTS: Among 10 enrolled patients, VSLI was escalated from 1.80 to 2.24 mg/m2, with one DLT (ileus) at 2.04 mg/m2. Two patients discontinued VSLI early. The most common AE included lymphopenia (100%), constipation, nausea, infusion reaction (each 60%), neutropenia, and peripheral neuropathy (50%). Grade 3/4 AE included lymphopenia (90%), neutropenia (20%), and ileus (10%), with prolonged grade ≥2 lymphopenia observed in most patients. Calculated MTD for VSLI was 2.25 mg/m2 (95% Bayesian credible interval: 2.00-2.40). Overall response was 100% with 50% CR. With median follow-up 26 months, 4/10 patients experienced recurrence and 1 died. CONCLUSION: Vincristine sulfate liposomal injection at 2.25 mg/m2 can be safely combined with BR for indolent B-cell lymphoma, but given observed toxicities and recurrences, we did not pursue an expanded cohort.Clinical Trials Registration Number: ClinicalTrials.gov identifier NCT02257242.

Use of naldemedine is associated with reduced incidence of hyperactive delirium in cancer patients with opioid-induced constipation: A nationwide retrospective cohort study in Japan.

BACKGROUND: Medical benefits of peripherally acting mu-opioid receptor antagonists other than improving opioid-induced constipation remain unclear. Our aim was to evaluate the association between the use of naldemedine and incidence of hyperactive delirium in cancer patients receiving chemotherapy and opioid therapy. METHODS: We conducted a propensity score-matched analysis using a nationwide inpatient database in Japan. Cancer patients receiving both inpatient chemotherapy and opioid therapy from June 1, 2017, to March 31, 2018, were included. Patients receiving naldemedine were matched to control patients by propensity score. Our primary outcome was the incidence of hyperactive delirium during hospitalization, and secondary outcomes were the length of hospital stay, hospital costs, in-hospital mortality, and incidence of ileus. RESULTS: Of 34,031 patients receiving inpatient chemotherapy and opioid therapy, 1905 (5.6%) were included in the naldemedine group. After one-to-four propensity score matching, 1904 patients were included in the naldemedine group and 7616 in the control group. Naldemedine users had significantly reduced incidence of hyperactive delirium compared with the control patients (19.4% vs 23.3%; risk difference, -3.9 [95% confidence interval, -5.9 to -1.9]; risk ratio, 0.83 [0.75-0.92]; p<0.001; subdistribution hazard ratio, 0.85 [0.75-0.97]; p = 0.015). The median length of hospital stay was significantly shorter in the naldemedine group compared with the control group (12 days [interquartile range, 6-23] vs 14 days [6-26]; p = 0.001). The median hospital costs were also significantly lower in the naldemedine group compared with the control group (US $6179 [3351-10,026] vs US $6576 [3436-11,107]; p < 0.001). No significant differences were found for in-hospital mortality or incidence of ileus between the groups. CONCLUSIONS: Our findings suggest that the use of naldemedine may have benefits in preventing hyperactive delirium, shortening hospital stay, and decreasing hospital costs in cancer patients receiving chemotherapy and opioid therapy.

Clinics in diagnostic imaging (201). Small bowel intramural haematoma induced by anticoagulation therapy with associated reactive ileus.

A 74-year-old woman receiving long-term anticoagulation with warfarin for chronic atrial fibrillation presented with severe acute abdominal pain, diarrhoea and vomiting. Initial laboratory workup revealed a deranged coagulation profile. Computed tomography of the abdomen and pelvis demonstrated spontaneous distal jejunal intramural haematoma with associated reactive ileus. No overt pneumatosis intestinalis, intraperitoneal free gas or haemoperitoneum was seen. Based on clinical and imaging findings, a diagnosis of over-anticoagulation complicated by small bowel intramural haematoma was made. The patient was managed non-operatively with analgesia, cessation of warfarin and reversal therapy with vitamin K. Warfarin therapy was recommenced upon resolution of symptoms and optimisation of coagulation status. The clinical presentation, radiological features and overall management of anticoagulation-induced bleeding are further discussed in this article.

Anti-TNF biologic therapy does not increase postoperative morbidity in pediatric Crohn's patients.

INTRODUCTION: Limited knowledge exists as to what impact preoperative biologic therapy has on postoperative complications in pediatric patients undergoing abdominal surgery for Crohn's disease (CD). Therefore, we sought to determine the 30-day postoperative infectious complication rate among pediatric CD patients who received biologic therapy within 12 weeks of an abdominal operation. METHODS: A retrospective chart review was performed on pediatric (<18 years of age) CD patients who underwent an abdominal operation between 1/1/2008 and 12/31/2017. Patients were grouped according to whether they received an anti-TNF (infliximab, adalimumab, certolizumab pegol) or no biologic therapy within 12 weeks prior to the operation. The primary outcome was the overall 30-day postoperative infectious complication rate. Secondary outcomes included 30-day readmission rate and return to the operating room (ROR). RESULTS: A total of 69 pediatric CD patients met inclusion criteria (n = 54 anti-TNF therapy, n = 15 received no biologic therapy). There were no differences between the anti-TNF and no biologic cohorts with respect to demographics or CD characteristics. No significant differences in overall 30-day postoperative infectious complications existed between patients exposed to anti-TNF agents and those with no preoperative exposure, or in its subcategories of surgical infectious complications and nonsurgical infectious complications. There was also no difference in the rate of ileus, readmission, or ROR. CONCLUSIONS: Preoperative exposure to anti-TNF biologic therapy does not add to overall or infectious 30-day postoperative morbidity in pediatric CD patients. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Retrospective review.

Treatment of vincristine-induced ileus with metoclopramide: A case report.

INTRODUCTION: Acute lymphoblastic leukemia is an invasive malignancy which ought to be treated with several cytotoxic medications. Vincristine-based regimen is among the most commonly used regimens for the treatment of adult acute lymphoblastic leukemia. Peripheral neuropathy caused by vincristine provides a limitation in dose administration and can influence the treatment outcome and patient's quality of life. CASE PRESENTATION: Ileus and constipation occurred as a result of autonomic neuropathy in a 58-year-old man who underwent vincristine-based regimen for acute lymphoblastic leukemia treatment. Despite the administration of several laxative agents for constipation, the complication did not improve. So metoclopramide as a prokinetic agent was administered intravenously, and patient bowel movement and defecation started after 24 h. CONCLUSIONS: There is no approved protocol for vincristine-induced autonomic neuropathy treatment; thus, prokinetic agents such as metoclopramide can be considered as an option for ileus treatment after ruling out the possibility of bowel obstruction. Prophylactic stool softeners should be administrated in all patients undergoing chemotherapy with vincristine to prevent gastrointestinal motility disorders.

Constipation, ileus and medication use during clozapine treatment in patients with schizophrenia in Iceland.

Purpose of the article: Clozapine is the only evidence based treatment for treatment-resistant schizophrenia. Constipation is a well known side effect of clozapine treatment. The aims of this study are to describe the prevalence of constipation and ileus during clozapine treatment of patients with schizophrenia in Iceland and to assess the concomitant use of medication that can cause constipation, and laxatives used to treat constipation. MATERIALS AND METHODS: We identified 188 patients treated with clozapine by searching the electronic health records of Landspitali, the National University Hospital, during the study period 1.1.1998 - 21.11.2014. Cases of constipation and ileus were identified using an electronic search with keywords related to ileus in the patients' electronic health records. Detailed medication use was available for 154 patients that used clozapine for at least one year. RESULTS: Four out of 188 patients were diagnosed with ileus that resulted in admission to hospital. Two of these required a permanent stoma as a consequence of their ileus. Laxatives were prescribed for 24 out of 154 patients (15.4%) while on clozapine. In total 40.9% of the patients either had laxatives prescribed or had constipation documented in the medical records. Apart from clozapine, other medications known to cause constipation were prescribed to 28 out of 154 patients (18.2%). CONCLUSIONS: Constipation is a common problem during clozapine treatment which can progress to full-blown ileus which can be fatal. Clinicians need to monitor signs of constipation during treatment with clozapine and respond to it with lifestyle advice and laxative treatment.

Postoperative complications of pediatric patients with inflammatory bowel disease treated with vedolizumab.

BACKGROUND: Vedolizumab is a biologic, which inhibits leukocyte adhesion in the gut and is used to treat ulcerative colitis (UC) and Crohn's disease (CD). Little is known of the surgical outcomes in patients treated with vedolizumab. We reviewed the postoperative complications in a cohort of pediatric UC and CD patients treated with vedolizumab. METHODS: We identified pediatric UC and CD patients treated with vedolizumab at our institution from 2014 to 2016. We compared postoperative outcomes in the vedolizumab exposed group to a cohort of vedolizumab naïve patients who required diverting ileostomy. RESULTS: Of the 31 patients who were treated with vedolizumab, 13 patients required surgery. Eight of 13 (62%) vedolizumab exposed patients had a postoperative complication, including mucocutaneous separation at the stoma (3), readmission for pain/dehydration (2), bowel obstruction at the ostomy, and intraoperative colonic perforation. In comparison, four of 16 (25%) vedolizumab naive patients had a postoperative complication, including readmission for ileus and for high stoma output with mucocutaneous separation. p=0.07. CONCLUSIONS: At our institution, patients treated with vedolizumab prior to surgery have a high prevalence of postoperative complications, notably mucocutaneous separation of the stoma. A prospective, multicenter study is needed to determine if these observed complications are attributable to vedolizumab. LEVEL OF EVIDENCE: Level III.

Decreased opioid consumption and enhance recovery with the addition of IV Acetaminophen in colorectal patients: a prospective, multi-institutional, randomized, double-blinded, placebo-controlled study (DOCIVA study).

BACKGROUND: We hypothesized that administration of IV acetaminophen alone would reduce the opioid consumption in post-operative colorectal surgery and reduce the side effects of narcotics. METHODS: Patients were randomized to receive either IV acetaminophen or placebo in addition to opioid PCA. Primary endpoints evaluated were opioid consumption and pain visual analogue scale score (PVASS) during first 48 h post-operatively. Secondary endpoints evaluated were time of return of GI function (ROGIF), time to diet ordered (TTDO), length of hospital stay (LOHS), and occurrence of ileus. RESULTS: 105 patients were enrolled and 97 remained in the study after exclusion (control group n = 50; study group n = 47). Mean ± SEs of opioid consumption in the study group was 21.5 ± 1.8 mg of morphine equivalent (ME) and 35.0 ± 3.3 mg ME at 24 and 48 h, respectively, versus 36.4 ± 4.1 mg ME and 59.7 ± 6.7 mg ME in the control group (p = 0.002 and 0.002). PVASS levels were lower in the study group at all intervals at 3, 8, 24, and 48 h (p = 0.02, 0.006, < 0.01, and 0.02). ROGIF, TTDO, and LOHS were also found to be lower in the study group (p ≤ 0.01, < 0.01, and 0.002). The rate of ileus was reduced by using IV acetaminophen (22% vs 2.1%; p = 0.004). CONCLUSIONS: IV acetaminophen helps to reduce opioid consumption for patients undergoing colorectal surgery. Additionally, there appears to be a shortened length of hospital stay, better pain control, reduced time to return of bowel function, and lower rate of post-operative ileus in patients receiving IV acetaminophen.

Objective evaluation of the systemic effects of topical application of 1% atropine sulfate ophthalmic solution in healthy horses.

OBJECTIVE To determine the safety of topical administration of 1% atropine ophthalmic solution in healthy horses by objectively measuring gastrointestinal transit time. DESIGN Randomized, masked, controlled crossover study. ANIMALS 6 adult geldings. PROCEDURES Horses were randomly assigned (3/group) to first receive topical treatment of the left eye with 1% atropine or artificial tears solution; the right eye was left untreated. After 24 hours of treatment every 6 hours, 200 nontoxic beads were administered to each horse via nasogastric intubation and treatment frequency was decreased to every 12 hours for 4 more days. Pupillary light reflexes (PLRs), mydriasis, heart rate, fecal bead passage, abdominal girth measurements, auscultable gut sounds, fecal weight, and clinical signs of abdominal pain were monitored. Following a 4-week washout period, horses received the opposite treatment in the left eye and measurements were repeated. Serum atropine concentration (reflecting systemic absorption) was measured with an ELISA at various points after initial atropine administration. RESULTS No horse had subjective or objective evidence of colic or ileus at any monitoring point. Complete mydriasis of the left eye with absence of the PLR was identified in 5 horses within 6 hours and in all 6 horses within 12 hours after initial atropine administration. One horse had mydriasis with an absent PLR in the untreated eye by day 5 of atropine treatment. At no point was atropine detected in serum samples of any horse. CONCLUSIONS AND CLINICAL RELEVANCE Topical atropine application at clinically appropriate doses induced no evidence of ileus in healthy horses.

Comparison of the effects of patient-controlled epidural and intravenous analgesia on postoperative bowel function after laparoscopic gastrectomy: a prospective randomized study.

BACKGROUND: Although laparoscopic surgery significantly reduces surgical trauma compared to open surgery, postoperative ileus is a frequent and significant complication after abdominal surgery. Unlike laparoscopic colorectal surgery, the effects of epidural analgesia on postoperative recovery after laparoscopic gastrectomy are not well established. We compared the effects of epidural analgesia to those of conventional intravenous (IV) analgesia on the recovery of bowel function after laparoscopic gastrectomy. METHOD: Eighty-six patients undergoing laparoscopic gastrectomy randomly received either patient-controlled epidural analgesia with ropivacaine and fentanyl (Epi PCA group) or patient-controlled IV analgesia with fentanyl (IV PCA group), beginning immediately before incision and continuing for 48 h thereafter. The primary endpoint was recovery of bowel function, evaluated by the time to first flatus. The balance of the autonomic nervous system, pain scores, duration of postoperative hospital stay, and complications were assessed. RESULTS: The time to first flatus was shorter in the epidural PCA group compared with the IV PCA group (61.3 ± 11.1 vs. 70.0 ± 12.3 h, P = 0.001). Low-frequency/high-frequency power ratios during surgery were significantly higher in the IV PCA group, compared with baseline and those in the epidural PCA group. The epidural PCA group had lower pain scores during the first 1 h postoperatively and required less analgesics during the first 6 h postoperatively. CONCLUSIONS: Compared with IV PCA, epidural PCA facilitated postoperative recovery of bowel function after laparoscopic gastrectomy without increasing the length of hospital stay or PCA-related complications. This beneficial effect of epidural analgesia might be attributed to attenuation of sympathetic hyperactivation, improved analgesia, and reduced opioid use.

Opioid-related side effects: Postoperative ileus, urinary retention, nausea and vomiting, and shivering. A review of the literature.

Opioids are widely used in clinical anesthesia. However, side effects include postoperative nausea and vomiting, shivering, ileus, and urine retention and are specifically discussed here. From the available evidence, it appears that the use of opioids is strongly associated with impaired gastrointestinal motility. Therefore, to prevent postoperative ileus, the use of opioids should be minimized and opioids should be replaced by other drugs. With regard to the risk of postoperative urinary retention, one problem is the lack of standardized definition. Nevertheless, the use of opioids is clearly an important risk factor. Postoperative nausea and vomiting have high incidences. Even if the mechanisms are partially understood, opioid-sparing strategies have been shown to decrease its incidence. Finally, the problem of postoperative shivering has been, at least partially, solved by the avoidance of (high doses) remifentanil and the use of alpha-2 agonists. In conclusion, postoperative urinary retention, postoperative ileus, nausea and vomiting, and shivering are complex problems seen after surgery. Management is possible, but prevention is possible with the avoidance of high doses of intraoperative opioids, conjointly to opioid-sparing techniques.

Rheumatoid arthritis triple therapy compared with etanercept: difference in infectious and gastrointestinal adverse events.

Objective: The main aim of this study was to examine the differences between triple therapy (T: SSZ and HCQ added to MTX) and etanercept (E) added to MTX with regard to the infectious and gastrointestinal (GI) adverse events (AEs) reported in The Rheumatoid Arthritis Comparison of Active Therapies Trial. Methods: The patients were 353 RA MTX incomplete responders who were randomized to T (n = 178) or E (n = 175). Of these, 88 patients were switched to the alternative treatment from the initial treatment (E or T) at 24 weeks per protocol. Infectious and GI serious AEs (SAEs) and non-serious AEs (NAEs) were reported during 48 and 4 weeks after the intervention period. Generalized linear models were used to estimate the incidence rate ratios (IRRs) of AEs between the two therapies. Results: Patients on E therapy were more likely to have infectious NAEs (IRR = 1.56, 95% CI: 1.11, 2.19). There was a greater number of infectious SAEs that occurred when patients received E than T therapy [12 E (6.9%) vs 4 T (2.2%), P = 0.19]. Pneumonia was the most common infectious SAE for both treatments [6 E (3.4%) and 2 T (1.1%)]. Conversely, patients who were on E were less likely to have GI NAEs than those on T therapy (IRR = 0.62, 95% CI: 0.40, 0.94). The most common GI SAE reported was GI haemorrhage, which occurred among three patients on E (1.7%). Conclusion: This study provides evidence of different likelihoods of infectious and GI AEs associated with two common, equally effective treatments for RA patients who have had incomplete responses to MTX. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov , NCT00405275.