Relationship between critical care nutrition and post-intensive care syndrome in surviving ventilated patients with COVID-19: a multicenter prospective observational study.

The impact of nutrition therapy in the acute phase on post-intensive care syndrome (PICS) remains unclear. We conducted a multicenter prospective study on adult patients with COVID-19 who required mechanical ventilation for more than three days. The questionnaire was mailed after discharge. Physical PICS, defined as less than 90 points on the Barthel index (BI), was assigned as the primary outcome. We examined the types of nutrition therapy in the first week that affected PICS components. 269 eligible patients were evaluated 10 months after discharge. Supplemental parenteral nutrition (SPN) >400 kcal/day correlated with a lower occurrence of physical PICS (10% vs 21.92%, p = 0.042), whereas the amounts of energy and protein provided, early enteral nutrition, and a gradual increase in nutrition delivery did not, and none correlated with cognitive or mental PICS. A multivariable regression analysis revealed that SPN had an independent impact on physical PICS (odds ratio 0.33, 95% CI 0.12-0.92, p = 0.034), even after adjustments for age, sex, body mass index and severity. Protein provision ≥1.2 g/kg/day was associated with a lower occurrence of physical PICS (odds ratio 0.42, 95% CI 0.16-1.08, p = 0.071). In conclusion, SPN in the acute phase had a positive impact on physical PICS for ventilated patients with COVID-19.

Prevalence and Risk Factor Analysis of Post-Intensive Care Syndrome in Patients with COVID-19 Requiring Mechanical Ventilation: A Multicenter Prospective Observational Study.

INTRODUCTION: Post-intensive care syndrome (PICS) is an emerging problem in critically ill patients and the prevalence and risk factors are unclear in patients with severe coronavirus disease 2019 (COVID-19). This multicenter prospective observational study aimed to investigate the prevalence and risk factors of PICS in ventilated patients with COVID-19 after ICU discharge. METHODS: Questionnaires were administered twice in surviving patients with COVID-19 who had required mechanical ventilation, concerning Barthel Index, Short-Memory Questionnaire, and Hospital Anxiety and Depression Scale scores. The risk factors for PICS were examined using a multivariate logistic regression analysis. RESULTS: The first and second PICS surveys were obtained at 5.5 and 13.5 months (mean) after ICU discharge, with 251 and 209 patients completing the questionnaires and with a prevalence of PICS of 58.6% and 60.8%, respectively, along with the highest percentages of cognitive impairment. Delirium (with an odds ratio of (OR) 2.34, 95% CI 1.1-4.9, and p = 0.03) and the duration of mechanical ventilation (with an OR of 1.29, 95% CI 1.05-1.58, and p = 0.02) were independently identified as the risk factors for PICS in the first PICS survey. CONCLUSION: Approximately 60% of the ventilated patients with COVID-19 experienced persistent PICS, especially delirium, and required longer mechanical ventilation.

Relation between nutrition therapy in the acute phase and outcomes of ventilated patients with COVID-19 infection: a multicenter prospective observational study.

BACKGROUND: Optimal nutrition therapy has not yet been established for the acute phase of severe coronavirus disease 2019 (COVID-19) infection. OBJECTIVES: We aimed to examine the effects of nutrition delivery in the acute phase on mortality and the long-term outcomes of post-intensive care syndrome (PICS). METHODS: A multicenter prospective study was conducted on adult patients with COVID-19 infection requiring mechanical ventilation during an intensive care unit (ICU) stay. Daily total energy (kcal/kg) and protein (g/kg) deliveries in the first week of the ICU stay were calculated. The questionnaire for PICS evaluation was mailed within a median of 6 mo after hospital discharge. The primary outcome was in-hospital mortality, and secondary outcomes were the PICS components of physical impairment, cognitive dysfunction, and mental illness. RESULTS: Among 414 eligible patients, 297 who received mechanical ventilation for 7 d or longer were examined. PICS was evaluated in 175 patients among them. High protein delivery on days 4-7 correlated with a low in-hospital mortality rate. In contrast, high protein delivery on days 1-3 correlated with physical impairment. A multivariate logistic regression analysis adjusted for age, sex, BMI, and severity revealed that average energy and protein deliveries on days 4-7 correlated with decreased in-hospital mortality (OR: 0.94; 95% CI: 0.89, 0.99; P = 0.013 and OR: 0.40; 95% CI: 0.17, 0.93; P = 0.031, respectively). Nutrition delivery did not correlate with PICS outcomes after adjustments. In the multivariate regression using a restricted cubic spline model, in-hospital mortality monotonically decreased with increases in average nutrition delivery on days 4-7. CONCLUSIONS: In patents with COVID-19 on mechanical ventilation for ≥7 d, nutrition delivery in the late period of the acute phase was monotonically associated with a decrease in in-hospital mortality. Adequate protein delivery is needed on days 4-7.This trial was registered at https://www.umin.ac.jp as UMIN000041276.

Usefulness of INTELLiVENT-ASV for postoperative ventilator-associated pneumonia: a case report.

BACKGROUND: INTELLiVENT®-ASV (iASV) is a respiration mode on the Hamilton G5. The ventilator uses a closed-loop mechanism that automatically adjusts settings related to oxygenation and ventilation. CASE PRESENTATION: A 47-year-old man underwent reconstruction surgery with free musculocutaneous flap for tongue resection. After surgery, the patient entered the ICU, and the iASV, which automatically changed only the percent minute volume (%MV) in respiration mode, was selected. On the second day, ventilator-associated pneumonia (VAP) was diagnosed, and the antibiotic treatment was changed. Using the settings of the iASV, automated FiO2 and positive end-expiratory pressure (PEEP) control were added to the ventilator mode. The patient's oxygenation was improved. CONCLUSIONS: In a patient who developed VAP after surgery, ventilation was continued using iASV, and automated changes in PEEP and FiO2 settings were successfully made according to the open lung strategy, under short-staffed circumstances.

Acute respiratory distress syndrome due to Strongyloides stercoralis infection in a patient with cervical cancer.

A 62-year-old woman complained of diarrhea and vomiting after receiving chemotherapy for cervical cancer in association with high doses of corticosteroids. Two months later, the patient developed acute respiratory distress syndrome, and numerous Strongyloides stercoralis parasites were found in the intrabronchial discharge. Ivermectin was administered daily until nematodes were no longer detected in the sputum, and the patient's condition was successfully rescued. Antibodies for human T-cell lymphotropic virus-1 (HTLV-1) were positive. HTLV-1 infection and the administration of corticosteroids are known risk factors for strongyloides hyperinfection syndrome. Therefore, physicians should consider this disease in the differential diagnosis of patients from endemic areas who present with gastrointestinal symptoms under these risk factors.

Vascular hyperpermeability in pulmonary decompression illness: 'the chokes'.

Decompression illness (DCI) develops during or after diving. Pulmonary decompression illness ('Chokes') is rarely seen because the affected individual usually dies in the water. We encountered a rare and interesting case. A 60-year-old man complained of leg pain after diving. Despite rapid transfer to a nearby hospital, advanced respiratory failure and shock had set in. He was then transferred to our hospital for hyperbaric oxygen therapy (HBOT). On account of his poor general condition, we initially treated him in the intensive care unit without HBOT, where he showed extreme hyperpermeability and a high level of serum procalcitonin (PCT; 20.24 ng/mL). Despite large-volume fluid therapy, severe intravascular dehydration and shock status remained. We assume that the injured endothelial cells induced vascular hyperpermeability and increased levels of inflammatory cytokines leading to the high serum PCT level. PCT might be a useful stress marker of endothelial damage and severity in DCI, including Chokes.

[Utility of target controlled infusion technique for deciding the fentanyl infusion rate for post-cholecystectomy pain management in a patient on anticoagulant therapy].

The fentanyl infusion rate was controlled by employing a target controlled infusion (TCI) technique under anticoagulant therapy for postoperative pain management. A 59-year-old woman with atrial fibrillation and mitral stenosis was scheduled for open cholecystectomy. Heparin was continuously infused for anticoagulant therapy. Sevoflurane and remifentanil were used for induction and maintenance of anesthesia. At completion of the operation, her consciousness was checked and the endotracheal tube was then removed under fentanyl TCI (effect-site concentration: Ce = 2.0 ng x ml(-1)). In this case, the spontaneous breathing rate was stable (10-12 x min(-1)) under fentanyl TCI. She had no complaints of pain(pain at rest: VAS 20 mm). The breathing rate in this case provided indication for postoperative pain management. The TIVAtrainer simulation makes the exchange from TCI infusion to continuous infusion easy. And the spontaneous breathing monitoring is useful for postoperative pain measurement of laparotomy cases.

[Ultrasound guidance facilitates arterial catheterization].

Ultrasound-guided arterial catheterization has been attempted, and its effectiveness demonstrated. We encountered 3 cases in which arterial catheterization (A-line) was difficult for the following reasons: the arterial lumen was narrow due to arteriosclerosis; the pulse of the radial artery was weak because of swelling in the arm and heart failure; and the deep artery was too hard for the needle to penetrate it. Using ultrasound guidance, arterial catheterization could be smoothly performed in all cases. Thus, ultrasound-guided arterial catheterization is effective for cases in which arterial catheterization using the usual palpation technique is difficult.

Spinal astrocyte glutamate receptor 1 overexpression after ischemic insult facilitates behavioral signs of spasticity and rigidity.

Using a rat model of ischemic paraplegia, we examined the expression of spinal AMPA receptors and their role in mediating spasticity and rigidity. Spinal ischemia was induced by transient occlusion of the descending aorta combined with systemic hypotension. Spasticity/rigidity were identified by simultaneous measurements of peripheral muscle resistance (PMR) and electromyography (EMG) before and during ankle flexion. In addition, Hoffman reflex (H-reflex) and motor evoked potentials (MEPs) were recorded from the gastrocnemius muscle. Animals were implanted with intrathecal catheters for drug delivery and injected with the AMPA receptor antagonist NGX424 (tezampanel), glutamate receptor 1 (GluR1) antisense, or vehicle. Where intrathecal vehicle had no effect, intrathecal NGX424 produced a dose-dependent suppression of PMR [ED50 of 0.44 microg (0.33-0.58)], as well as tonic and ankle flexion-evoked EMG activity. Similar suppression of MEP and H-reflex were also seen. Western blot analyses of lumbar spinal cord tissue from spastic animals showed a significant increase in GluR1 but decreased GluR2 and GluR4 proteins. Confocal and electron microscopic analyses of spinal cord sections from spastic animals revealed increased GluR1 immunoreactivity in reactive astrocytes. Selective GluR1 knockdown by intrathecal antisense treatment resulted in a potent reduction of spasticiy and rigidity and concurrent downregulation of neuronal/astrocytic GluR1 in the lumbar spinal cord. Treatment of rat astrocyte cultures with AMPA led to dose-dependent glutamate release, an effect blocked by NGX424. These data suggest that an AMPA/kainate receptor antagonist can represent a novel therapy in modulating spasticity/rigidity of spinal origin and that astrocytes may be a potential target for such treatment.

Transcranial motor-evoked potentials monitoring can detect spinal cord ischemia more rapidly than spinal cord-evoked potentials monitoring during aortic occlusion in rats.

In this study, we evaluated the efficacy of transcranial motor-evoked potentials (tc-MEPs), compared with segmental spinal cord-evoked potentials (SCEPs), for detecting spinal cord ischemia (SCI) and assessed the relationship between neurological outcome and tc-MEPs or SCEPs in the rat aortic occlusion model. In the rats, SCI was induced by aortic occlusion for 10 min with a balloon catheter. At first, tc-MEPs (Group A: n = 6) or segmental SCEPs (Group B: n = 6) was recorded during SCI. Second, in using the quantal bioassay for the relationship between an interval of aortic occlusion and the probability of positive response in tc-MEPs or segmental SCEPs, the P50(MEP) and P50(SCEP) which represent the interval of aortic occlusion associated with 50% probability of assessment of ischemic spinal cord dysfunction by tc-MEP and SCEP were analyzed. The amplitude of tc-MEPs decreased significantly at 30 s and disappeared completely at 2 min after aortic occlusion. In Group B, it took about 6 min after aortic occlusion to diminish SCEP signal amplitude by approximately 50%. P50(MEP) obtained in the quantal analysis was 0.3 +/- 0.1 min. P50(SCEP) was calculated as 6.2 +/- 0.5 min that was significantly (P < 0.01) longer than P50(MEP). Our data indicated that tc-MEP monitoring could detect the onset of SCI so rapidly in comparison with segmental SCEP monitoring, which could provide therapeutic windows in a surgical approach that includes spinal cord protection.

Development of baclofen tolerance in a rat model of chronic spasticity and rigidity.

Systemic or spinal treatment with baclofen has been associated with the development of tolerance in patients with chronic spasticity. In the present study, we used a rat model of spinal ischemia-induced spasticity to characterize the development of baclofen tolerance after chronic intrathecal (i.t.) baclofen infusion. Following the induction of spinal ischemia and the development of behavioral spasticity, animals were implanted with i.t. catheters connected to osmotic pumps to continuously infuse baclofen (1.0 microg/0.5 microl/h). Hindleg peripheral muscle resistance (PMR) was measured periodically after initiation of chronic infusion and after bolus i.t. baclofen injection (1.0 microg). Peripheral muscle resistance was significantly decreased at the onset of baclofen infusion, however, after 5-7 days of infusion a progressive return of spasticity was noted, where baseline PMR values returned to preinfusion levels. At the same time, the efficacy of bolus i.t. baclofen treatment also decreased, where after 5 days of baclofen infusion 1.0 microg (i.t.) baclofen only reduced PMR by 10% (compared to 40-50% preinfusion). Baclofen efficacy progressively returned once continuous infusion was stopped. These data demonstrate that transient spinal ischemia leads to the development of spasticity which is sensitive to spinal baclofen. Chronic i.t. infusion leads to a progressive development of tolerance. This model offers potential to study tolerance mechanisms after spinal injury, and aid in drug discovery for use in baclofen-tolerant patients.

Aberrant halt of syringe pump motion: an improved system to prevent false setting of the syringe.

A syringe pump is used to inject precise doses of drugs having a strong action; for example, vasoactive drugs. Unexpected and undetected halt of a syringe pump can lead to potentially life-threatening complications. We experienced a sudden halt in the movement of a syringe pump (Terufusion syringe pump; Terumo, Tokyo, Japan) in two patients while administering norepinephrine in the intensive care unit (ICU). Fortunately, the patients had only transient hypotension, which was immediately detected and promptly treated, without any untoward sequelae. As a result of the occurrence of such cases, we conducted a detailed investigation of the causes of this sudden halt in the syringe pump. We could not reproduce the aberration of the syringe pump and thus could not specify the cause in the first patient. In the second patient, however, a false setting on the syringe was suspected to be the cause of the problem. In order to prove this, we tried to reproduce the situation where a syringe pump, due to a false syringe setting, abruptly terminated while giving a "syringe loss" warning, after a period of precise functioning. Once we had determined how a false setting of the syringe could occur without the syringe pump giving off an alarm from the onset, we collaborated with the Terumo Company to revise their current instruction manual to incorporate this as a warning. We also helped in the development of a new model, including a new safety feature that would prevent a false setting of the syringe from occurring at all. This new model was released in December 2003.

Influence of the descending thoracic aortic cross clamping on bispectral index value and plasma propofol concentration in humans.

BACKGROUND: In this study, the authors investigated changes in Bispectral Index (BIS) values and plasma propofol concentrations (Cp) after aortic cross clamping in the descending thoracic aortic aneurysm repair surgery during propofol anesthesia. METHODS: Prospectively, in 10 patients undergoing thoracic aortic surgery during total intravenous anesthesia with propofol, BIS values were recorded during cross clamping of the descending thoracic aorta. In this study, the rate of propofol infusion was controlled to keep the BIS value between 30 and 60 throughout surgery. Simultaneously, Cp values in the blood samples taken from the right radial artery (area proximal to cross clamping) and the left femoral artery (area distal to cross clamping) were measured. RESULTS: Approximately 15 min after initiating aortic cross clamping, BIS values in all cases started to decrease abruptly. Cp values of samples taken from the radial artery after cross clamping of the aorta were significantly (P < 0.05) increased compared with pre-cross clamp values (1.8 +/- 0.4 microg/ml), and the mean Cp after aortic cross clamping varied between 3.0 and 5.3 microg/ml. In addition, there were significant differences in the Cp values between radial arterial and femoral arterial blood samples throughout aortic cross clamping. Cp values in samples from the radial artery were approximately two to seven times higher than those from the femoral artery. CONCLUSIONS: This study showed that Cp values increased and BIS values decreased rapidly after aortic cross clamping in thoracic aortic aneurysm repair surgery during propofol anesthesia. These findings suggested that all anesthesiologists should control the infusion rate carefully, taking the abrupt changes in its pharmacokinetics into consideration, especially during cross clamping of the descending thoracic aorta.

Intrathecal nicorandil and small-dose morphine can induce spastic paraparesis after a noninjurious interval of spinal cord ischemia in the rat.

We investigated the interaction between nicorandil, a K(+)ATP channel opener, and morphine on motor function after a noninjurious interval of spinal cord ischemia in the rat. Spinal ischemia was induced by aortic occlusion for 6 min with a balloon catheter in Sprague-Dawley rats. All animals received intrathecal (IT) injection of morphine (1-60 microg) 1 h after ischemia. In addition to IT injection of morphine, group M (control), group MN (combination of morphine and nicorandil), and group MNG (combination of morphine, nicorandil, and glibenclamide) received IT saline, nicorandil (10 microg), and both glibenclamide (10 microg) and nicorandil (10 microg) after 150 min of reperfusion, respectively. A quantal bioassay for the effect of IT morphine on neurological function after ischemia was performed to calculate 50% effective dose values (ED50) for inducing paraparesis at 3 h of reperfusion. The ED50 in group M and group MN was 15.1 +/- 4.9 microg and 2.9 +/- 1.0 microg of IT morphine, respectively (P < 0.05). In Group MNG, the dose-response curve shifted back to the right and the ED50 for inducing paraparesis was 11.6 +/- 4.7 microg of IT morphine. The present study demonstrates that IT small-dose morphine combined with nicorandil induces spastic paraparesis after noninjurious interval of spinal cord ischemia in the rat.

Unanticipated full stomach at anesthesia induction in a type I diabetic patient with asymptomatic gastroparesis.

We encountered a case of unanticipated full stomach at anesthesia induction, despite a 12-h fasting period, in a type I diabetes patient with diabetic neuropathy presenting for elective vitrectomy for proliferative diabetic retinopathy. The patient had ingested seaweed 24 h prior to the surgery, and it was later found in the aspirated gastric content. Gastrointestinal dysfunction due to diabetic neuropathy and the high fiber content of the ingested seaweed are the probable causes of unanticipated full stomach in our case.

Intrathecal administration of morphine, but not small dose, induced spastic paraparesis after a noninjurious interval of aortic occlusion in rats.

UNLABELLED: We sought to investigate the dose-response relationship for the effect of intrathecal morphine on the transient spastic paraparesis after short-lasting spinal ischemia in rats. Spinal ischemia was induced by aortic occlusion for 6 min with a balloon catheter in rats previously implanted with an intrathecal catheter for drug delivery. After ischemia, the animals were allowed to recover, and 3, 10, or 30 microg of morphine or saline was injected intrathecally at 30 min after reperfusion. In a separate group, the quantal bioassay for the effect of intrathecal morphine on neurological function after ischemia was performed to calculate 50% effective dose values for inducing paraparesis at 2 h of reperfusion. Subsequently, histopathology of the spinal cord was assessed at 48 h of reperfusion. Intrathecal injection of 30 or 10 micro g of morphine, but 3 micro g of neither morphine nor saline, caused a progressive development of hindlimb spasticity. The 50% effective dose values for inducing paraparesis were 16.1 +/- 1.5 microg in assessing behavioral analysis at 2 h after intrathecal morphine. Histopathological analysis of spinal cords in the 30- microg group revealed the presence of dark-staining alpha-motoneurons in lumbosacral segments. We conclude that spinal administration of a large dose of morphine after transient aortic occlusion may be associated with a potential risk of paraparesis and the corresponding development of neurological dysfunction. Careful attention should be paid when intrathecal morphine is used for pain control after thoracoabdominal aortic aneurysm repair. IMPLICATIONS: Spinal administration of large-dose morphine after transient aortic occlusion may be associated with a potential risk of irreversible spinal neuronal degeneration and the corresponding development of neurological dysfunction.

Propofol reduces spinal motor neuron excitability in humans.

IMPLICATIONS: We investigated in humans whether changes in spinal motor neuron excitability correlate with the predicted propofol concentration (Cpt) achieved by a target-controlled infusion system. Propofol suppressed F-wave persistence in a Cpt-dependent manner, indicating that propofol depresses spinal motor neuron excitability at clinically relevant concentrations.