Patient participation and associated factors in the discussions on do-not-attempt-resuscitation and end-of-life disclosure: a retrospective chart review study.

BACKGROUND: Patient participation is a key foundation of advance care planning (ACP). However, a patient himself/herself may be left out from sensitive conversations such as end-of-life (EOL) care discussions. The objectives of this study were to investigate patients' participation rate in the discussion of Cardiopulmonary Resuscitation (CPR) / Do-Not-Attempt-Resuscitation (DNAR) order, and in the discussion that the patient is at his/her EOL stage (EOL disclosure), and to explore their associated factors. METHODS: This is a retrospective chart review study. The participants were all the patients who were hospitalized and died in a university-affiliated teaching hospital (tertiary medical facility) in central Tokyo, Japan during the period from April 2018 to March 2019. The following patients were excluded: (1) cardiopulmonary arrest on arrival; (2) stillbirth; (3) under 18 years old at the time of death; and (4) refusal by their bereaved family. Presence or absence of CPR/DNAR discussion and EOL disclosure, patients' involvement in those discussions, and their associated factors were investigated. RESULTS: CPR/DNAR discussions were observed in 336 out of the 358 patients (93.9%). However, 224 of these discussions were carried out without a patient (patient participation rate 33.3%). Male gender (odds ratio (OR) = 2.37 [95% confidence interval (CI) 1.32-4.25]), living alone (OR = 2.51 [1.34-4.71]), and 1 year or more from the date of diagnosis (OR = 1.78 [1.03-3.10]) were associated with higher patient's participation in CPR/DNAR discussions. The EOL disclosure was observed in 341 out of the 358 patients (95.3%). However, 170 of the discussions were carried out without the patient (patient participation rate 50.1%). Patients who died of cancer (OR = 2.41[1.45-4.03]) and patients without mental illness (OR=2.41 [1.11-5.25]) were more likely to participate in EOL disclosure. CONCLUSIONS: In this clinical sample, only up to half of the patients participated in CPR/DNAR discussions and EOL disclosure. Female, living with family, a shorter period from the diagnosis, non-cancer, and mental illness presence are risk factors for lack of patients' participation in CPR/DNAR or EOL discussions. Further attempts to facilitate patients' participation, based on their preference, are warranted.

Retraction Note: Desflurane anesthesia worsens emergence agitation in adult patients undergoing thyroid surgery compared to sevoflurane anesthesia.

The Editor-in-Chief has retracted this article [1]. The ethics committee approval was granted for an observational study and the need for patient consent was waived. However, the study design described is a randomized controlled trial and therefore patient consent should have been obtained. All authors agree with this retraction.

Aberrant resting-state functional connectivity of the dorsolateral prefrontal cortex to the anterior insula and its association with fear avoidance belief in chronic neck pain patients.

Chronic neck pain (CNP), a global health problem, involves a large amount of psychological and socioeconomic burdens. Not only physical causes but also behavioral disorders such as a fear-avoidance belief (FAB) can associate with the chronicity of neck pain. However, functional brain mechanisms underlying CNP and its related behavioral disorders remain unknown. The aim of the current resting-state functional magnetic resonance imaging (fMRI) study was to explore how the functional brain networks differed between CNP patients and age- and sex-matched healthy, pain-free controls (HCs). We also investigated whether these possible brain network changes in CNP patients were associated with fear avoidance belief (FAB) and the intensity of pain. We analyzed the resting-state fMRI data of 20 CNP patients and 20 HCs. FAB and the intensity of pain were assessed by Tampa Scale for Kinesiophobia (TSK) and Visual Analog Scale (VAS) of pain. The whole brain analysis showed that CNP patients had significant different functional connectivity (FC) compared with HCs, and the right dorsolateral prefrontal cortex (DLPFC) was a core hub of these altered functional networks. Furthermore, general linear model analyses showed that, in CNP patients, the increased FC between the right DLPFC and the right anterior insular cortex (aIC) significantly associated with increased TSK (p = 0.01, statistical significance after Bonferroni correction: p<0.025), and the FC between the right DLPFC and dorsal posterior cingulate cortex had a trend of inverse association with VAS (p = 0.04). Our findings suggest that aberrant FCs between the right DLPFC and aIC associated with CNP and its related FAB.

Perioperative Factors Associated With Chronic Central Pain After the Resection of Intramedullary Spinal Cord Tumor.

OBJECTIVE: Some patients experience severe chronic pain after intramedullary spinal cord tumor (IMSCT) resection, but the underlying mechanisms have yet to be fully elucidated. We aimed to investigate perioperative factors associated with chronic pain after IMSCT resection. MATERIALS AND METHODS: We analyzed data from a postal survey and the medical records of patients who had undergone IMSCT resection in our institution between 2000 and 2008. Chronic pain was assessed using the Neuropathic Pain Symptom Inventory score, and its associations with factors related to tumor pathology, patient demographics, neurological findings, surgery, anesthesia, and perioperative management were determined. RESULTS: Seventy-eight consecutive patients (55 men and 23 women; age 17 to 79 y) were included in the statistical analysis of the present study. In univariate analyses, sex, body mass index, preoperative tumor-related pain, preoperative nonsteroidal anti-inflammatory drugs, intraoperative hypotension, postoperative corticosteroids, and decrease in Japanese Orthopaedic Association (JOA) scores were found to be associated with postsurgical chronic central pain. Logistic regression analysis identified 3 significant factors: a decline in JOA scores compared with preoperative values (odds ratio [OR], 3.33; 95% confidence interval [CI], 1.18-9.42; P=0.023), intraoperative hypotension (OR, 3.01; 95% CI, 1.02-8.97; P=0.047), and postoperative corticosteroids (OR, 3.21; 95% CI, 1.02-10.09; P=0.046). DISCUSSION: Decline in JOA score, intraoperative hypotension, and postoperative corticosteroids are independently associated with postsurgical chronic central pain. Intraoperative hypotension and the use of postoperative corticosteroids can be avoided or modified during perioperative management. As results from animal studies have indicated that the administration of corticosteroids may intensify chronic pain, further studies in larger cohorts are required to definitively determine the effect of corticosteroids on postsurgical central pain.

Desflurane anesthesia worsens emergence agitation in adult patients undergoing thyroid surgery compared to sevoflurane anesthesia.

BACKGROUND: The effect of volatile anesthetics on emergence agitation in adults remains unclear. We compared the degree of emergence agitation between desflurane and sevoflurane anesthesia in adults undergoing thyroid surgery. FINDINGS: One hundred and sixteen patients with American Society of Anesthesiologists status 1 or 2 were randomized into two groups: the desflurane group (group D) and the sevoflurane group (group S). After induction of anesthesia with fentanyl (1-2 µg/kg) and propofol (1.5-2.5 mg/kg), tracheal intubation was facilitated with suxamethonium (0.5-1.0 mg/kg). In group D, anesthesia was maintained with desflurane in 66% nitrous oxide and 33% oxygen supplemented with fentanyl when necessary; in group S, sevoflurane was used instead of desflurane. After the end of the surgery, emergence agitation was evaluated with a modified pediatric anesthesia emergence delirium scale (ranging from 0 to 16, with higher scores indicating more severe emergence agitation) before extubation. Time to extubation from the end of the surgery, postoperative pain (evaluated by a numerical rating scale [NRS]), and postoperative nausea and vomiting (PONV) after surgery were examined. The degree of emergence agitation was more severe in group D than in group S (median [interquartile range]: 5 [4-7] vs 4 [2-6], p = 0.008). Time to extubation, NRS scores, and PONV rates were similar between the two groups. CONCLUSIONS: Desflurane anesthesia worsened emergence agitation as compared with sevoflurane in adult patients undergoing thyroid surgery, but did not affect time to extubation, postoperative pain, or PONV. TRIAL REGISTRATION: UMIN000014215.

[Difficult Perioperative Glucose Management in a Type 2 Diabetic Patient with Anti-insulin Antibody Undergoing Laparoscopic Partial Liver Resection].

A 50-year-old man with type 2 diabetes mellitus was scheduled for laparoscopic partial liver resection. Six months prior to the surgery, he developed frequent hypoglycemic attacks and was diagnosed as anti-insulin antibody positive. The operation was performed under general anesthesia with epidural anesthesia. Intermit- tent and continuous insulin administration was required during liver resection due to persistent hyperglycemia. After termination of the liver resection, the patient exhibited uncontrolled hypo- and hypergly- cemia, and recovery from anesthesia was delayed due to severe hypoglycemia. He recovered immediately after 40% glucose administration. However, frequent glucose administration was required for two hours after transfer to the ICU due to hypoglycemia. It should be born in mind that preoperative poor glucose control might be caused by anti-insulin antibodies and lead to difficult perioperative glucose management.

Neutrophil gelatinase-associated lipocalin regulates gut microbiota of mice.

BACKGROUND AND AIM: Because neutrophil gelatinase-associated lipocalin (NGAL) is known to provide significant bacteriostatic effects during infectious conditions, we tested the hypothesis that this protein is up-regulated and secreted into the intraluminal cavity of the gut under critically ill conditions and is thus responsible for the regulation of bacterial overgrowth. METHODS: With our institutional approval, male C57BL/6J mouse (6-7 weeks) were enrolled and applied for lipopolysaccharide or peritonitis model compared with naïve control. We assessed NGAL protein concentrations in intestinal lumen and up-regulation of NGAL expression in intestinal tissues in in vivo as well as ex vivo settings. Simultaneously, we examined the effects of NGAL protein administration on the growth of Escherichia coli (E. coli) in in vivo and in vitro experimental settings. The localization of NGAL in intestinal tissues and lumen was also assessed by immunohistological approach using NGAL antibody. RESULTS: Both lipopolysaccharide and peritonitis insults evoked the marked up-regulation of NGAL mRNA and protein levels in gut tissues such as crypt cells. In addition, the administration of NGAL protein significantly inhibited the outgrowth of enteric E. coli under both in vitro and in vivo conditions, accompanied by histological evidence. CONCLUSION: Neutrophil gelatinase-associated lipocalin protein accompanied by apparent bacteriostatic action accumulated in the intestinal wall and streamed into the mucosal layer during critically ill state, thereby possibly shaping microbiota homeostasis in the gut.

Long-term outcomes of percutaneous radiofrequency thermocoagulation of gasserian ganglion for 2nd- and multiple-division trigeminal neuralgia.

OBJECTIVES: The objective of this study was to examine the long-term outcome of percutaneous radiofrequency thermocoagulation (PRT) of the Gasserian ganglion for the 2nd division and multiple division trigeminal neuralgia (TN), compared to the isolated 3rd division TN. METHODS: One hundred and forty-eight procedures performed in 89 patients with typical TN between April 2004 and September 2011 in a single pain center were retrospectively analyzed. Baseline characteristics of these patients, immediate outcome, duration pain-free, and complications were obtained from their medical records and questionnaires sent in June 2012. Duration pain-free was assessed by Kaplan-Meier analysis. RESULTS: Of the 148 PRT of the Gasserian ganglion, 37 procedures were performed for isolated 2nd-division TN (V2 TN), 67 procedures were for both 2nd- and 3rd-division TN (V2 + V3 TN), and 38 procedures were for isolated 3rd-division TN (V3 TN). The remaining 6 procedures were performed for V1 + V2 TN and V1 + V2 + V3 TN. Immediate success rates of PRT for V2 TN, V2 + V3 TN, and V3 TN were 100%, 86.6%, and 100%, respectively, whereas the durations pain-free for V2 TN and V2 + V3 TN were significantly shorter than that for V3 TN (9, 12, and 36 months, respectively: P = 0.012). CONCLUSION: For 2nd-division TN and multiple-division TN, less long-term pain relief after PRT of the Gasserian ganglion can be expected compared with that for isolated trigeminal 3rd-division neuralgia, even if immediate pain relief is achieved.

Questionnaire survey on current status of home care and support for patients with hematological diseases.

In order to survey the current status of home care and support for patients with hematological diseases, questionnaires were sent to 3,591 hospitals and home care facilities in Tokyo and surrounding prefectures. The first survey showed that 81.7% of medical staff members at hospitals reported that they had experience with home care and support, but only 24.9% of home care facility staff members had such experience. The second questionnaire, surveying 1,202 personnel, identified four factors hampering successful establishment of home care and support networks for hematological diseases. These included insufficient familial support for patients, difficulty making end of life decisions by family members and patients, limited access to transfusion support, and financial problems.

Symptoms overlooked in hospitalized cancer patients: Impact of concurrent symptoms on oversight [corrected] by nurses.

OBJECTIVE: Physical and psychological symptoms in cancer patients are frequently overlooked by medical staff. However, little is known regarding the potential impacts of concurrent physical and psychological symptoms on the overlooking of other symptoms. The aim of this study was to examine the impact of concurrent symptoms on the overlooking of other symptoms in cancer inpatients. METHOD: A total of 255 cancer inpatients in the general wards of one university hospital, who were referred to the palliative care team, were included. On the day of referral, nurses and patients were independently assessed for the presence of the following eight symptoms: pain, fatigue, nausea and vomiting, shortness of breath, lack of appetite, dry mouth, sleep problems, and distressed feelings. The presence of delirium was also separately assessed by nurses and psychiatrists on the team. A total of nine symptoms detected by nurses and those reported by patients or psychiatrists were compared, and logistic regression analysis was performed to identify the variables associated with the overlooking of these symptoms. RESULTS: The most frequently reported symptom was pain (76.5%), followed by distressed feelings (49.8%), sleep problems (34.1%), and delirium (25.1%). The proportion of those overlooked was more than one quarter (25.0-63.6%) for all symptoms except pain (12.8%). Significant associations were found between the overlooking of shortness of breath and concurrent delirium (odds ratio [OR] = 110.9); the overlooking of sleep problems and concurrent lack of appetite (OR = 9.1); and the overlooking of distressed feelings and concurrent dry mouth (OR = 27.7). No patient demographic characteristic was associated with the overlooking of any other symptoms. SIGNIFICANCE OF RESULTS: The presence of some specific concurrent symptoms is likely to lead to the overlooking of other symptoms in cancer inpatients by nurses. Comprehensive assessments of physical and psychological symptoms in daily clinical practice are needed.

Incidence and risk factors of postoperative delirium in patients with esophageal cancer.

BACKGROUND: Postoperative delirium is a common complication after major surgery and is characterized by acute confusion with fluctuating consciousness. The aim of this study was to investigate the incidence and risk factors of postoperative delirium in patients with esophageal cancer. METHODS: We conducted a retrospective cohort analysis of 306 consecutive patients who had undergone an esophagectomy at Keio University Hospital from January 1998 to December 2009. All data were assessed by psychiatrists, and delirium was diagnosed according to criteria of the Diagnostic and Statistical Manual Disorder, fourth edition. Univariate and multivariate analyses were performed. RESULTS: Postoperative delirium developed in 153 (50.0 %) of 306 patients. One hundred fourteen (37.3 %) of the 306 patients required psychoactive medication for symptoms associated with delirium. Univariate analyses showed that older age, male gender, additional flunitrazepam for sedation in intensive care unit (ICU) after surgery, longer periods of time under mechanical ventilation after surgery, longer ICU stays, occurrence of postoperative complications, and longer hospital stays were significantly associated with postoperative delirium. Multivariate analysis revealed that development of delirium was linked to older age, additional flunitrazepam in ICU, and occurrence of postoperative complication. CONCLUSIONS: The development of postoperative delirium in patients with esophageal cancer is a problem that cannot be ignored. Our results suggest that the risk of developing delirium is associated with older age, use of flunitrazepam in ICU, and postoperative complications.

Retrospective evaluation of intravenous fentanyl patient-controlled analgesia during labor.

PURPOSE: Because the safety of intravenous fentanyl patient-controlled analgesia (iv-PCA) administered during labor remains unclear, we retrospectively examined the labor records from January 2005 to December 2007 in our institution, with a focus on both maternal and neonatal outcomes, as compared to no analgesia. METHODS: Parturients over 35 weeks of gestational age who received fentanyl iv-PCA (iv-PCA group) or no analgesia (control group) during labor were enrolled. The former group received iv-PCA through a pump programmed to give a loading dose of 0.05 mg fentanyl, followed by bolus injection of 0.02 mg fentanyl, with a lock-out interval of 5 min. This analgesia was initiated at the parturient's request and was discontinued before the second stage of labor, to ensure neonatal safety. During labor, both maternal and fetal heart rates, maternal pulse oximeter oxygen saturation (SpO(2)), respiratory rate, and sedation and nausea scores were continuously monitored, and the neonatal outcomes including umbilical arterial pH, Apgar scores, and other parameters were recorded. RESULTS: The data of 129 of the 143 parturients who received fentanyl iv-PCA were analyzed, while 697 parturients delivered without any analgesia during the 3-year study period. While iv-PCA prolonged the duration of labor and increased oxytocin use, no obvious maternal or neonatal complications of fentanyl use were recorded. Except for the significantly lower rate of emergency cesarean section in the iv-PCA group, both the maternal and neonatal outcomes were comparable between the groups. CONCLUSIONS: As compared to no analgesia, fentanyl iv-PCA appears to be safe and clinically acceptable as analgesia during labor, particularly in nulliparous women.

[Postoperative analgesia for hepatic cryosurgery].

BACKGROUND: Hepatic cryosurgery is an alternative therapeutic choice for patients who are not eligible for surgical liver resection. As this procedure sometimes causes postoperative bleeding tendency, we investigated indication of intravenous patient-controlled analgesia (IVPCA) after this surgery. METHODS: We measured pre- and postoperative platelet counts, coagulation profile and postoperative pain with IVPCA in 8 patients. RESULTS: Platelet counts decreased from 9.83 +/- 5.38 (x 10(3) x ml(-1)) to 5.91 +/- 4.56 (x10(3) x ml(-1)) postoperatively (P<0.01) and the maximum relative decrease was 72%. Platelet counts reached the maximum depression from 1 to 3 POD and in two patients it did not recover by 7 POD. Percentage of prothrombin activity decreased from 79.5 +/- 10.4 to 65.9 +/- 13.2 (P<0.01), with the nadir observed from 0 POD to 2 POD. In this study it was difficult to predict the extent of postoperative bleeding tendency beforehand. IVPCA with morphine provided adequate analgesia at rest. Althogh pain on moving seemed rather difficult to treat in two patients, IVPCA also helped patients walk with VAS score less than 55 mm in other patients. CONCLUSIONS: Considering the risk of bleeding tendency and epidural hematoma, we recommend IVPCA with opioid for postoperative pain in patients after hepatic cryosurgery instead of epidural analgesia and non-steroidal anti-inflammatory drugs.

Unmet supportive needs of cancer patients in an acute care hospital in Japan--a census study.

PURPOSE: Little research has been done on supportive needs of cancer patients in acute hospitals in Japan. This study aims to comprehensively assess the unmet supportive needs of hospitalized cancer patients, as well as literacy and utilization of appropriate professional care. METHODS: All cancer patients (aged 20 to 80 years) who were hospitalized in a university hospital in Tokyo during the designated 3-day period between September 1 and October 31, 2007 were recruited for participation in the study. The M.D. Anderson Symptom Inventory, Brief Cancer-Related Worry Inventory, and Hospital Anxiety and Depression Scale were administered. Patients' knowledge and use of relevant services were evaluated. The results were compared with those of non-cancer patients in the same treatment settings. RESULTS: A total of 125 cancer patients and 59 non-cancer patients were enrolled. Cancer patients and non-cancer patients equally suffered from physical symptoms (15-26% had severe appetite loss, 18-19% had severe dry mouth, and 16-22% had severe pain); however, psychological distress of cancer patients exceeded that of non-cancer patients (28.0% vs 8.5%; p ≤ 0.05). Severe psychological distress was associated with severe worry about future prospects or interpersonal and social issues and presence of two or more severe symptoms. Two thirds of the patients with severe psychological distress knew about the psychiatric division, but only one third actually sought treatment. CONCLUSIONS: Needs related to psychological issues were more prevalent among cancer patients than among non-cancer patients, despite a similar level of physical distress. Special attention should be paid to cancer patients who worry over future prospects or interpersonal and social issues, and those who have two or more severe symptoms.

Hypercapnic acidosis minimizes endotoxin-induced gut mucosal injury in rabbits.

OBJECTIVE: Recent evidence demonstrated that hypercapnic acidosis due to lung protective strategy was not only permissive but also even therapeutic for injured lung. Since the effects of hypercapnic acidosis on extra-pulmonary organs remain to be clarified, we tested the hypothesis that hypercapnic acidosis protects gut mucosal barrier function by modulating inflammation in a rabbit model of endotoxemia. DESIGN: Prospective randomized animal study. SETTING: University research laboratory. SUBJECTS: Male New Zealand white rabbits. INTERVENTIONS: Thirty-two animals were randomly allocated into two groups: normocapnia (n = 17) and hypercapnia (n = 15). The latter group received F(I)CO(2) 5% under mechanical ventilation to achieve hypercapnia throughout the study periods, whereas the former with F(I)CO(2) 0%. MEASUREMENTS AND RESULTS: Arterial blood gas, intramucosal pH (pHi) and portal blood flow were assessed at baseline, 2-h and 4-h infusion of lipopolysaccharide. At 4 h, ileal myeloperoxidase (MPO) activity and intestinal permeability were measured. The animals in the hypercapnia group showed apparent hypercapnic acidosis and progressive intramucosal acidosis at 4 h, accompanied by significantly lower intestinal permeability versus normocapnia group. Ileal MPO activity was comparable between the study groups. CONCLUSIONS: Hypercapnic acidosis attenuates endotoxin-induced gut barrier dysfunction possibly through neutrophil-independent mechanisms.

Effects of morphine and its metabolites on immune function in advanced cancer patients.

STUDY OBJECTIVE: To determine whether morphine and its active metabolites such as morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) modulate immune function in patients with advanced cancer who required morphine for pain relief. DESIGN: Prospective observational clinical study. SETTING: Pain clinic of a university hospital. PATIENTS: Fifteen patients who visited our clinic for control of advanced cancer pain. INTERVENTIONS: During the initiation or changes of morphine therapy, venous blood samples were obtained at the enrollment of this study, 1 and 3 weeks after the change of morphine dose or route. MEASUREMENTS: Lymphocyte subpopulation CD4+ and CD8+, activity of natural killer cell, phytohemagglutinin (PHA)-induced T-cell proliferation, and plasma immunoglobulin M and G concentrations were measured, as well as plasma concentrations of morphine, M-3-G, and M-6-G. MAIN RESULTS: At the entry of the study, 6 patients did not receive any type of morphine medication (group 1), whereas 9 patients were treated with morphine for 1 month (group 2). Cancer pain, rated as 4 at the entry period, was reduced to 2 of 10 (visual analogue scale) during the study periods. Although the plasma concentrations of M-3-G and M-6-G in Group 1 were significantly less than those in Group 2, plasma concentrations of immunologic markers were similar between the groups. In Group 1, Spearman linear regression analysis showed negative correlation between morphine-derived metabolites and immunoglobulins or PHA-induced T-cell proliferation, whereas poor correlation was found with all immunologic parameters in Group 2. Stepwise linear regression analyses showed that the metabolites, rather than morphine per se, modulated immune function, reflected by PHA-induced T-cell proliferation and immunoglobulin G concentration in Group 1. CONCLUSIONS: The present study suggests that some of humoral and cellular immunity are modulated by morphine-derived metabolites at the early phase of morphine therapy in patients with advanced cancer.