Point-of-care testing for tranexamic acid efficacy: a proof-of-concept study in cardiac surgical patients.

BACKGROUND: Low-dose tranexamic acid (TXA) has been recently recommended for cardiopulmonary bypass (CPB) to reduce associated complications. Although point-of-care laboratory tests for TXA concentrations are unavailable, a novel TPA-test on the ClotPro® system can measure TXA-induced inhibition of fibrinolysis. We evaluated the performance of the TPA-test in vitro and in patients undergoing surgery requiring CPB. METHODS: Blood samples were obtained from six volunteers for in vitro evaluation of tissue plasminogen activator (tPA)-triggered fibrinolysis and the effects of TXA. This was followed by an observational study in 20 cardiac surgery patients to assess clinical effects of TXA on the TPA-test. RESULTS: Hyperfibrinolysis induced by tPA was inhibited by TXA ≥2 mg L-1 in a concentration-dependent manner, and was completely inhibited at TXA ≥10 mg L-1. In patients undergoing CPB, antifibrinolytic effect was detectable on TPA-test parameters after a 0.1 g bolus of TXA at the end of CPB, and complete inhibition of fibrinolysis was obtained with TXA ≥0.5 g. The antifibrinolytic effects of 1 g TXA on TPA-test parameters were gradually attenuated over 18 h after surgery. However, the fibrinolytic inhibition continued in four patients with estimated glomerular filtration rate (eGFR) ≤30 ml min-1 1.73 m-2. The eGFR had strong correlations with TPA-test parameters at 18 h after surgery (r=0.86-0.92; P<0.0001). CONCLUSIONS: The TPA-test is sensitive to low concentrations of TXA and serves as a practical monitoring tool for postoperative fibrinolytic activity in cardiac surgery patients. This test might be particularly useful in patients with severe renal impairment.

Post-intensive care syndrome: Recent advances and future directions.

Post-intensive care syndrome comprises physical, cognitive, and mental impairments in patients treated in an intensive care unit (ICU). It occurs either during the ICU stay or following ICU discharge and is related to the patients' long-term prognosis. The same concept also applies to pediatric patients, and it can greatly affect the mental status of family members. In the 10 years since post-intensive care syndrome was first proposed, research has greatly expanded. Here, we summarize the recent evidence on post-intensive care syndrome regarding its pathophysiology, epidemiology, assessment, risk factors, prevention, and treatments. We highlight new topics, future directions, and strategies to overcome post-intensive care syndrome among people treated in an ICU. Clinical and basic research are still needed to elucidate the mechanistic insights and to discover therapeutic targets and new interventions for post-intensive care syndrome.

Fixing the anesthesia research crisis in Japan.

To explore the current status of anesthesia research activity in Japan, we analyzed the number of abstracts presented at the Japanese Society of Anesthesiologists (JSA) annual meetings by several factors including gender, society branches, and subspecialty categories. The number of abstracts at JSA annual meetings has declined sharply since 2016 with no gender gap. A decrease in the neurological field predated the overall decline, but other subspecialty categories showed a similar decline. Although the Tokyo, Tokai-Hokuriku, and Kyushu branches were responsible for more than half of the reduction, the trend was similar among all branches. In a survey regarding academic activities of university hospital residents and faculty, Ph.D. aspirants' rate was only 20-30%. Residents had never presented an abstract at scientific conferences and never published any papers at nearly 40% and 30% of the university hospitals, respectively. Our survey suggests that junior anesthetists are losing interest in research. Senior faculty and mentors must redouble efforts to embed and encourage research in departments and by anesthetists in training. If a revival of anesthesia research in Japan does not occur then a service only specialty awaits.

Efficacy and safety of intravenous fosphenytoin for patients with acute herpes zoster-associated pain: A placebo-controlled randomized trial.

Acute zoster-associated pain develops in most patients with herpes zoster. Nonopioid analgesics are usually used to treat acute zoster-associated pain but are frequently ineffective. We administered intravenous fosphenytoin, the prodrug of phenytoin, to patients with acute zoster-associated pain to examine its analgesic efficacy and safety. At 13 medical institutions in Japan, we conducted a phase II, double-blind, placebo-controlled, randomized trial of intravenous fosphenytoin in Japanese inpatients with acute zoster-associated pain for whom nonopioid analgesics had shown an insufficient analgesic effect. The patients were randomly assigned (1:1:1) to receive a single intravenous dose of fosphenytoin at 18 mg/kg (high dose), a single intravenous dose of fosphenytoin at 12 mg/kg (low dose), or placebo. The primary endpoint was the mean change per hour (slope) in the numerical rating scale score from the baseline score until 120 min after dosing. Seventeen patients were randomly assigned to the low-dose fosphenytoin group (n = 6, median age 62.5 years, range 39-75 years), high-dose fosphenytoin group (n = 5, median age 69.0 years, range 22-75 years), and placebo group (n = 5, median age 52.0 years, range 38-72 years). One patient was excluded because of investigational drug dilution failure. This study was discontinued because of the influences of coronavirus disease 2019. The slope was significantly lower in the high- and low-dose fosphenytoin groups than in the placebo group (P < 0.001 and P = 0.016, respectively). Responsiveness to intravenous fosphenytoin (≥2-point reduction in the numerical rating scale score from baseline to 120 min after dosing) was inferred at plasma total phenytoin concentrations of 10-15 µg/mL. Treatment-emergent adverse events caused no safety concerns in the clinical setting and intravenous fosphenytoin was well tolerated. Intravenous fosphenytoin appears to be an effective and promising alternative treatment for acute zoster-associated pain. Trial Registration: ClinicalTrials.gov NCT04139330.

Effect of acute normovolemic hemodilution in patients undergoing cardiac surgery with remimazolam anesthesia.

PURPOSE: The reduced effects of allogeneic transfusion with acute normovolemic hemodilution (ANH) have been reported. Harvesting a large volume of blood may maximize the effect in patients with low body weight, and the prevention of hypotension is important. Remimazolam is an anesthetic with few circulatory responses. Our aim was to evaluate whether high-volume ANH reduces the need for transfusion in cardiac patients under remimazolam anesthesia. METHODS: In this retrospective single-center study, we enrolled cardiopulmonary bypass (CPB) patients who received remimazolam anesthesia. Changes in hemodynamic parameters were assessed. The numbers of blood transfusions and chest tube outputs were also evaluated. RESULTS: In a total of 51 patients, ANH was performed in 27 patients with a mean body mass index of 23.2 (ANH volume: 740 ± 222 mL). No significant differences were observed in mean blood pressure during blood collection. The intraoperative amount of red blood cell (RBC) transfusion was significantly lower in the ANH group than in the control group (431 ± 678 and 1260 ± 572 mL, p < 0.001). The avoidance rates of RBC were 66.7 and 4.2%, respectively. The multivariate analysis result revealed that ANH correlated with RBC, with an odds ratio of 0.067 (95% confidence interval 0.005-0.84, p < 0.05). The postoperative bleeding at 24 h was significantly lower in the ANH group (455 ± 228 and 797 ± 535 mL, p < 0.01). CONCLUSION: In patients undergoing CPB, ANH reduced intraoperative transfusion amount and postoperative bleeding. Hemodynamic changes during blood collection were minimal under remimazolam anesthesia and high-volume ANH was feasible.

Molecular characterization of wild-type and HSAN2B-linked FAM134B.

BACKGROUND: Family with sequence similarity 134, member B (FAM134B), also known as Reticulophagy regulator 1 (RETREG1), is an ER-phagy receptor involved in ER homeostasis. Congenital mutations in the FAM134B gene have been reported to be associated with hereditary sensory and autonomic neuropathy type 2B (HSAN2B); however, the molecular differences between wild-type and HSAN2B-linked FAM134B are not fully understood. METHODS AND RESULTS: We prepared several human FAM134B constructs, such as the HSAN2B-linked mutant, and compared their features with those of wild-type FAM134B by transfecting these constructs into FAM134B-deficient Neuro2a cells. Although intrinsic FAM134B protein expression in wild-type Neuro2a cells was affected by the supply of amino acids in the culture medium, the expression of each HSAN2B-linked mutant FAM134B protein was hardly affected by serum and amino acid deprivation. On the other hand, the intracellular localization of GFP-tagged HSAN2B-linked mutants, except for P7Gfs133X, overlapped well with ER-localized SP-RFPKDEL and did not differ from that of GFP-tagged wild-type FAM134B. However, analysis of protein‒protein interactions using the NanoBiT reporter assay revealed the difference between wild-type and C-terminal truncated mutant FAM134B. Furthermore, this NanoBiT assay demonstrated that both wild-type and G216R FAM134B interacted with LC3/GABARAPL1 to the same extent, but the FAM134B construct with mutations near the LC3-interacting region (LIR) did not. Similar to the NanoBiT assay, the C-terminal-truncated FAM134B showed lower ER-phagy activities, as assessed by the cotransfection of GFP-tagged reporters. CONCLUSIONS: We showed that wild-type and HSAN2B-linked FAM134B have different molecular characteristics by transfecting cells with various types of constructs. Thus, this study provides new insights into the molecular mechanisms underlying HSAN2B as well as the regulation of ER-phagy.

Long Duration of Action of Tranexamic Acid After Cardiac Surgery in a Hemodialysis Patient: A Case Report.

A 61-year-old woman with chronic renal dysfunction was scheduled to undergo aortic valve replacement. After a bolus of 1 g tranexamic acid (TXA), the TPA (tissue-plasminogen activator)-test result with the ClotPro system demonstrated extensive inhibition of fibrinolysis. Plasma TXA level decreased from 71 to 25 µg/dL at 6 hours postoperatively; however, no further decrease was observed. Although TXA levels dropped to 6.9 µg/dL after hemodialysis on postoperative day (PoD) 1, fibrinolytic shutdown on the TPA-test remained unchanged until PoD 2. In dialysis patients, low-dose TXA <1 g may be considered for reducing seizure and thromboembolic complications after cardiac surgery.

Prevalence of preoperative opioid usage and its impact on postoperative outcomes: a retrospective cohort study.

PURPOSE: Preoperative opioid treatment increases postoperative adverse events. This study was aimed to analyze preoperative opioid prevalence in countries with low opioid consumption. Additionally, the effect of low opioid usage on postoperative outcomes was also investigated. METHODS: We conducted this single center retrospective cohort analysis in a Japanese university-affiliated hospital to investigate opioid usage and its impact on the duration of postoperative hospitalization and in-hospital mortality. Adult patients who underwent general anesthesia between 2015 and 2020 were included. We extracted the patients' characteristics, surgical information and postoperative outcomes. Subgroup analysis to address opioid dose effect was performed in high and low dose opioid subgroups. RESULTS: Among 20,306 inpatients, 535 (2.63%) patients used opioids preoperatively. Tramadol was the most frequently used opioid. The median morphine equivalent (MME) dose was 15 mg/day. Median duration of hospitalization was 18 and 9 days in the opioid and non-opioid groups, and in-hospital mortality was 2.06% and 0.42%. Multivariable regression analysis demonstrated that preoperative opioid use was associated with a longer duration of hospitalization and in-hospital mortality. Subgroup analysis demonstrated longer durations of hospitalization in both high (> 30 mg/day MME) and low (≤ 30 mg/day MME) dose opioid groups, while higher in-hospital mortality was seen only in the high dose opioid group. CONCLUSIONS: Preoperative opioid usage was one-tenth of the United States average. Despite its low prevalence and small dosage, preoperative opioid usage was associated with poor postoperative outcomes. Dedicated perioperative interventions to prevent opioid-associated adverse events should be developed even in countries with low opioid consumption.

Activation of neurons and satellite glial cells in the DRG produces morphine-induced hyperalgesia.

Activation of neurons and glial cells in the dorsal root ganglion is one of the key mechanisms for the development of hyperalgesia. The aim of the present study was to examine the role of neuroglial activity in the development of opioid-induced hyperalgesia. Male rats were treated with morphine daily for 3 days. The resultant phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in the dorsal root ganglion was analyzed by immunohistochemistry and Western blotting. Pain hypersensitivity was analyzed using behavioral studies. The amount of cytokine expression in the dorsal root ganglion was also analyzed. Repeated morphine treatment induced hyperalgesia and marked induction of phosphorylated ERK1/2 in the neurons and satellite glial cells on day 3. An opioid receptor antagonist, toll like receptor-4 inhibitor, MAP/ERK kinase (MEK) inhibitor and gap junction inhibitor inhibited morphine-induced hyperalgesia and ERK1/2 phosphorylation. Morphine treatment induced alteration of cytokine expression, which was inhibited by the opioid receptor antagonist, toll like receptor-4 inhibitor, MEK inhibitor and gap junction inhibitor. Dexamethasone inhibited morphine-induced hyperalgesia and ERK1/2 phosphorylation after morphine treatment. The peripherally restricted opioid receptor antagonist, methylnaltrexone, inhibited hyperalgesia and ERK1/2 phosphorylation. Morphine activates ERK1/2 in neurons and satellite glial cells in the dorsal root ganglion via the opioid receptor and toll like receptor-4. ERK1/2 phosphorylation is gap junction-dependent and is associated with the alteration of cytokine expression. Inhibition of neuroinflammation by activation of neurons and glia might be a promising target to prevent opioid-induced hyperalgesia.

A comparison of the ClotPro system with rotational thromboelastometry in cardiac surgery: a prospective observational study.

Viscoelastic coagulation tests have been increasingly used for hemostasis management in cardiac surgery. The ClotPro system is a novel viscoelastic device based on principles of rotational thromboelastometry. We aimed to compare ClotPro with ROTEM and plasma coagulation assays in cardiopulmonary bypass (CPB) patients. Blood samples were collected from 25 CPB patients at (1) baseline, (2) start of CPB, (3) end of CPB, and (4) end of surgery. The EX-test, IN-test, HI-test, FIB-test parameters on ClotPro were compared with corresponding ROTEM assay (EXTEM, INTEM, HEPTEM, and FIBTEM). Standard plasma coagulation assays and endogenous thrombin generation (TG) were simultaneously evaluated. Pearson correlation analyses showed moderate correlations between clotting times (CTs) (r = 0.63-0.67; p < 0.001, respectively), and strong correlations with maximal clot firmness (MCF) (r = 0.93-0.98; p < 0.001, respectively) between ClotPro and ROTEM. EX-test and IN-test MCF parameters were interchangeable with acceptable percentage errors (EX-test MCF: 7.3%, IN-test MCF: 8.3%), but FIB-test MCF (27.0%) and CT results were not (EX-test CT: 44.7%, IN-test CT: 31.4%). The correlations of PT/INR or peak TG with EX-test CTs were higher than with EXTEM CTs (PT/INR: r = 0.80 and 0.41, peak TG: 0.43 and 0.18, respectively). FIB-test MCF has strong correlation with plasma fibrinogen and factor XIII level (r = 0.84 and 0.66, respectively). ROC analyses showed that ClotPro was capable of emulating well-established ROTEM thresholds (area under curves: 0.83-1.00). ClotPro demonstrated strong correlations in MCF parameters of ROTEM in CPB patients. It may be reasonable to modify ROTEM-based transfusion algorithm pertaining to MCF parameters to establish cut-off values for ClotPro device.

Localization of Chronic Pain in Postmastectomy Patients: A Prospective Comparison Between Patients With and Without Breast Reconstruction.

BACKGROUND: After breast surgery with or without immediate reconstruction, chronic pain can be a major problem for patients. However, few studies have examined the details of the sites of long-lasting postoperative pain. In this study, we specified the postoperative pain location after breast surgery, including reconstruction, to find ways to improve surgical procedures or provide effective pain relief. METHODS: The subjects were 205 Japanese women undergoing mastectomy or breast reconstruction with a tissue expander (TE)/implant or a deep inferior epigastric perforator (DIEP) flap. Patients were asked whether they had pain in different parts of the body at 1 year after surgery. Differences were assessed by cross-tabulation and χ2 statistics. RESULTS: Surveys were completed by 157 subjects. Deep inferior epigastric perforator flap cases had significantly more pain and TE/Imp cases had significantly less pain in the medial breast, upper breast, breast upper medial quadrant, and abdomen (P = 0.006, P = 0.006, P < 0.001, P < 0.001, respectively). In the neck area, pain in TE/Imp cases was significantly worse than that in all other patients (P = 0.025). There was no significant difference in chronic pain in any other body regions among the mastectomy only, TE/Imp, and DIEP flap groups. CONCLUSIONS: The results of the present study revealed that the localization of prolonged postoperative pain after breast surgery differs depending on the surgical procedure. In DIEP flap reconstruction, there was a marked tendency for pain in the inner and upper chest and in the abdomen, whereas TE/IMP surgery resulted in pain around the neck of the affected side. These findings may help improve surgical methods and establish effective pain relief that focuses on the identified pain areas.

IGF1-driven induction of GPCR kinase 2 in the primary afferent neuron promotes resolution of acute hyperalgesia.

Dynamic regulation of G-protein-coupled receptor (GPCR) kinase 2 (GRK2) expression restores cellular function by protecting from overstimulation via GPCR and non-GPCR signaling. In the primary afferent neurons, GRK2 negatively regulates nociceptive tone. The present study tested the hypothesis that induction of GRK2 in the primary afferent neurons contributes to the resolution of acute pain after tissue injury. GRK2 expression in the dorsal root ganglion (DRG) was analyzed at 1 and 7 days after the incision. Intraperitoneal administration of a GRK2 inhibitor was performed 7 days post-incision in male Sprague-Dawley rats who underwent plantar incisions to analyze the pain-related behavioral effect of the GRK2 inhibitor. Separately, GRK2 expression was analyzed after injecting insulin-like growth factor 1 (IGF1) into the rat hind paw. In addition, an IGF1 receptor (IGF1R) inhibitor was administered in the plantar incision rats to determine its effect on the incision-induced hyperalgesia and GRK2 expression. Plantar incision induced an increase in GRK2 in the DRG at 7 days, but not at 1 day post-incision. Acute hyperalgesia after the plantar incision disappeared by 7 days post-incision. Intraperitoneal injection of the GRK2 inhibitor at this time reinstated mechanical hyperalgesia, although the GRK2 inhibitor did not produce hyperalgesia in naive rats. After the incision, IGF1 expression increased in the paw, but not in the DRG. Intraplantar injection of IGF1 increased GRK2 expression in the ipsilateral DRG. IGF1R inhibitor administration prevented both the induction of GRK2 and resolution of hyperalgesia after the plantar incision. These findings demonstrate that induction of GRK2 expression driven by tissue IGF1 has potent analgesic effects and produces resolution of hyperalgesia after tissue injury. Dysregulation of IGF1-GRK2 signaling could potentially lead to failure of the spontaneous resolution of acute pain and, hence, development of chronic pain after surgery.

Usefulness of bicarbonate Ringer's solution as perfusate during transurethral resection of the prostate.

Transurethral resection of the prostate (TURP) is the most common standard surgical procedure used for benign prostatic hyperplasia. Transurethral resection in saline (TURis) is a bipolar electrosurgery system used to prevent TURP (or TUR) syndrome. The bicarbonate Ringer's solution is not generally used as perfusate for TURP. Hence, we compared the efficacy of the bicarbonate Ringer's solution with that of physiological saline as perfusate during TURP. This prospective, multicenter, cooperative study was conducted on 40 adult patients admitted to a medical college hospital. After obtaining informed consent from all the patients, they were divided into two groups (20 patients per group). For patients of one group, bicarbonate Ringer's solution, and for other group, physiological saline was used as perfusate. Compared to the physiological saline, the electrolyte composition of the bicarbonate Ringer's solution was closer to that of plasma. Hence, the group using bicarbonate Ringer's solution as perfusate was exhibited less variation in plasma electrolytes and blood gas data. The primary endpoints were adverse events of grade 1 or higher according to the JCOG postoperative complication criteria ver. 2.0, unintended diseases, or related signs in patients who underwent the protocol therapy. The secondary endpoints were changes in blood pH, bicarbonate ion level, anion gap (AG), base excess (BE), and chloride (C1), which occurred during and after the surgeries. Therefore, bicarbonate Ringer's solution has superior with that of physiological saline as perfusate during TURP which is directly administered into the blood vessels as an infusion solution.Bicarbonate Ringer's solution is directly administered into the blood vessels as an infusion solution.

Extensive Lumbar Sympathetic Ganglion Block Combined With Epidural Block for Primary Erythromelalgia: A Case Report.

A 19-year-old-woman experienced severe burning pain in the lower extremities with erythema and swelling. She was diagnosed with primary erythromelalgia (PE). The pain was unresponsive to medications but relieved by immersing her feet in cold water. We performed a multilevel lumbar sympathetic ganglion block (LSGB) with 5% phenol at second lumbar vertebra (L2) and third lumbar vertebra (L3), and additional fourth lumbar vertebra (L4) levels. An epidural block was intermittently combined. The pain and skin lesions dramatically improved after the procedures, and she no longer needed medications or to soak her feet in cold water. This case demonstrated that extensive LSGB may be a therapeutic option for intractable PE.

Spinal and Peripheral Mechanisms Individually Lead to the Development of Remifentanil-induced Hyperalgesia.

The present study was performed to determine neuronal loci and individual molecular mechanisms responsible for remifentanil-induced hyperalgesia. The effect of methylnaltrexone (MNX) on remifentanil-induced behavioral hyperalgesia was assessed to distinguish contributions of the peripheral and/or central nervous system to remifentanil-induced hyperalgesia. Phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) in the dorsal root ganglion (DRG) neurons after remifentanil infusion, and the effect of a p38MAPK inhibitor on remifentanil-induced hyperalgesia were analyzed to investigate involvement of p38MAPK in the peripheral mechanisms of remifentanil-induced hyperalgesia. Spinal levels of prodynorphin mRNA after remifentanil infusion, and the effect of the BK2 bradykinin receptor antagonist on remifentanil-induced hyperalgesia were investigated to assess potential spinal mechanisms. The effects of MNX and BK2 antagonists on remifentanil-induced exacerbation of post-incisional hyperalgesia were also investigated using behavioral analysis. Remifentanil infusion induced hyperalgesia in the early (4 h to 2 days) and late (8-14 days) post-infusion periods. MNX inhibited hyperalgesia only during the early post-infusion period. p38MAPK phosphorylation was observed in the DRG neuron, and the p38MAPK inhibitor inhibited hyperalgesia during the early post-infusion period. Prodynorphin expression increased in the spinal cord, and a BK2 antagonist inhibited hyperalgesia during the late post-infusion period. Remifentanil-induced exacerbation of incisional hyperalgesia was inhibited by MNX and the BK2 antagonist. The present study demonstrated that remifentanil activates peripheral and spinal neurons to promote chronologically distinctive hyperalgesia. p38MAPK phosphorylation in the DRG neuron leads to peripherally-driven hyperalgesia during the early post-infusion period, while spinal dynorphin-bradykinin signaling promotes hyperalgesia during the late post-infusion period.

Factors associated with chronic pain following breast reconstruction in Japanese women.

Chronic pain after breast surgery including breast reconstruction is a major concern for patients. However, the factors associated with chronic pain after breast surgery are uncertain in Japanese population. The aim of this study was to identify patient-specific and medical/surgical factors that predict chronic pain after breast surgery in Japanese patients. The subjects were 189 Japanese women undergoing breast surgery including tissue expander/implant (TE/implant), deep inferior epigastric perforator (DIEP) procedures and mastectomy only. Pain was assessed at one year postoperatively using a validated survey instrument: the Japanese version of the Short-Form McGill Pain Questionnaire (SF-MPQ-JV). A multiple linear regression model was used to examine the relationships of clinical factors with postoperative pain. Surveys were completed by 141 subjects. A younger age (p = .04) and bilateral procedures (p < .05) were both closely associated with the extent of increased postoperative pain at 1 year using the MPQ-Total pain rating. Compared to total mastectomy only, TE/implant procedures showed a significantly lower visual analog scale (VAS) (p = .04) and present pain index (PPI) (p = .03) scores. No factor related to chronic pain was also significantly related to the frequency of pain medication use postoperatively or the effect of social life of the patients. This study identified patients at risk for greater chronic pain after breast surgery. These findings will allow surgeons to improve patient comfort, reduce clinical morbidity and enhance patient satisfaction with their surgical outcome. Abbreviations: BMI: body mass index; CI: confidence interval; DIEP: deep inferior epigastric perforator flap; MPQ: McGill pain questionnaire; PPI: present pain index; SD: standard deviation; SF-MPQ-JV: Japanese version of the short-form McGill pain questionnaire; TE: tissue expander; VAS: visual analog scale.

Factors related to memory absence and delusional memories in patients in intensive care units managed with light sedation.

OBJECTIVES: Currently, light sedation is typically given to patients in intensive care units and studies have not extensively examined the factors related to absences or abnormalities of their memories. We, therefore, analysed the factors related to the absence/abnormalities of patients' memories in intensive care units. RESEARCH METHODOLOGY: A secondary analysis of previously collected survey data examining patients' experiences in an intensive care unit was undertaken (n = 405; women = 38%; median age = 70 years). To observe absent or distorted memories, patients were interviewed after leaving the intensive care unit. We analysed key factors through content analysis of the interviews and field notes. SETTING: The intensive care unit of a university hospital. MAIN OUTCOME MEASURE: Patients' absent or distorted memories after leaving the intensive care unit. RESULTS: Half the patients reported an absence of memories. This was associated with old age and with longer duration of mechanical ventilation. Absent or fragmentary memories were not distressing. Fragmentary and fearful intensive care unit memories were associated with being older. Delusional memories, some of which reflected actual events, were present in 3% of patients. CONCLUSION: Absence of memories were not distressing, delusional memories occurred less and these memories could comprise of an event in ICU that is difficult for patients to understand.

Reduction of the rocuronium-induced withdrawal reflex by MR13A10A, a generic rocuronium with a novel solution: A randomized, controlled study.

BACKGROUND: Rocuronium induces venous pain and the withdrawal reflex during injection. MR13A10A, generic rocuronium with a novel solution, reduced the injection-induced withdrawal reflex in rodents. We hypothesized that MR13A10A would reduce the frequency and severity of injection-induced withdrawal reflexes compared with original rocuronium during clinical anesthesia induction. METHODS: This prospective, open (but assessor-blinded), randomized, controlled study was conducted at a single academic hospital. The assessor was blinded to the study condition in order to minimize observer bias. Participants were allocated to either MR13A10A or traditional formula groups by a blocked stratified randomization method. Participants in the MR13A10A group received MR13A10A, whereas the original rocuronium group received the same amount of original rocuronium. The primary outcome was presence of the withdrawal reflex after rocuronium injection. Severity of the withdrawal reflex, changes in blood pressure and heart rate, and the train of four (TOF) ratio were measured as secondary outcomes. The withdrawal reflex was assessed using a video recording in a blinded manner. RESULTS: Of the 149 participants, 76 were allocated to the MR13A10A group and 73 to the original rocuronium group. The frequency of the withdrawal reflex was significantly lower with MR13A10A compared with original rocuronium (19.7% and 54.8% for MR13A10A and original rocuronium groups, respectively, p<0.001). The odds ratio adjusted for cannulation site, cannula size, induction agent and age was 6.27 (95% CI, 2.87, 13.73 p<0.001). Original rocuronium was an independent factor related to a higher post-treatment heart rate. The proportions of TOF ratios = 0 were similar between the two groups. CONCLUSION: The frequency and severity of the withdrawal reflex after injection were significantly reduced by using MR13A10A. MR13A10A might contribute to safe and less invasive anesthesia management.