Abnormal magnesium levels and their impact on death and acute kidney injury in critically ill children.

BACKGROUND: The prevalence of magnesium imbalance in critically ill children is very high. However, its significance in the development of acute kidney injury (AKI) and mortality remains unknown. METHODS: In this retrospective observational study from 2010 to 2018, the pediatric-specific intensive care database was analyzed. We included critically ill children aged > 3 months and those without chronic kidney disease. Patients were diagnosed with AKI, according to the Kidney Disease Improving Global Outcomes (KDIGO) study. We calculated the initial corrected magnesium levels (cMg) within 24 h and used a spline regression model to evaluate the cut-off values for cMg. We analyzed 28-day mortality and its association with AKI. The interaction between AKI and magnesium imbalance was evaluated. RESULTS: The study included 3,669 children, of whom 105 died within 28 days, while 1,823 were diagnosed with AKI. The cut-off values for cMg were 0.72 and 0.94 mmol/L. Both hypermagnesemia and hypomagnesemia were associated with 28-day mortality (odds ratio [OR] = 2.99, 95% confidence interval [CI] = 1.89-4.71, p < 0.001; OR = 2.80, 95% CI = 1.60-4.89, p < 0.001). Hypermagnesemia was associated with AKI (OR = 1.52, 95% CI = 1.27-1.82, p < 0.001), while neither hypermagnesemia nor hypomagnesemia interacted with the AKI stage on the 28-day mortality. CONCLUSIONS: Abnormal magnesium levels were associated with 28-day mortality in critically ill children. AKI and hypermagnesemia had a strong association. "A higher resolution version of the Graphical abstract is available as Supplementary information".

Near-infrared spectroscopy monitoring during out-of-hospital cardiac arrest: can the initial cerebral tissue oxygenation index predict ROSC?

STUDY OBJECTIVES: Near-infrared spectroscopy is a modality that can monitor tissue oxygenation index (TOI) and has potential to evaluate return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR). This study's objectives were to evaluate whether TOI could be associated with ROSC and used to help guide the decision to either terminate CPR or proceed to extracorporeal CPR (ECPR). METHODS: In this observational study, we assessed the patients with out-of-hospital cardiac arrest with non-traumatic cause receiving CPR on arrival at our ED between 2013 and 2016. TOI monitoring was discontinued either on CPR termination after ROSC was reached or on patient death. Patients were classified into two groups: ROSC and non-ROSC group. RESULTS: Out of 141 patients, 24 were excluded and the remaining 117 were classified as follows: ROSC group (n=44) and non-ROSC group (n=73). ROSC group was significantly younger and more likely to have their event witnessed and bystander CPR. ROSC group showed a higher initial TOI than non-ROSC group (60.5%±17.0% vs 37.9%±13.7%: p<0.01). Area under the curve analysis was more accurate with the initial TOI than without it for predicting ROSC (0.88, 95% CI 0.82 to 0.95 vs 0.79, 95% CI 0.70 to 0.87: p<0.01). TOI cut-off value ≥59% appeared to favour survival to hospital discharge whereas TOI ≤24% was associated with non-ROSC. CONCLUSIONS: This study demonstrated an association between higher initial TOI and ROSC. Initial TOI could increase the accuracy of ROSC prognosis and may be a clinical factor in the decision to terminate CPR and select patients who are to proceed to ECPR.

Human mannose-binding lectin inhibitor prevents Shiga toxin-induced renal injury.

Hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC HUS) is a worldwide endemic problem, and its pathophysiology is not fully elucidated. Here we tested whether the mannose-binding lectin (MBL2), an initiating factor of lectin complement pathway activation, plays a crucial role in STEC HUS. Using novel human MBL2-expressing mice (MBL2 KI) that lack murine Mbls (MBL2(+/+)Mbl1(-/-)Mbl2(-/-)), a novel STEC HUS model consisted of an intraperitoneal injection with Shiga toxin-2 (Stx-2) with or without anti-MBL2 antibody (3F8, intraperitoneal). Stx-2 induced weight loss, anemia, and thrombocytopenia and increased serum creatinine, free serum hemoglobin, and cystatin C levels, but a significantly decreased glomerular filtration rate compared with control/sham mice. Immunohistochemical staining revealed renal C3d deposition and fibrin deposition in glomeruli in Stx-2-injected mice. Treatment with 3F8 completely inhibited serum MBL2 levels and significantly attenuated Stx-2 induced-renal injury, free serum hemoglobin levels, renal C3d, and fibrin deposition and preserved the glomerular filtration rate. Thus, MBL2 inhibition significantly protected against complement activation and renal injury induced by Stx-2. This novel mouse model can be used to study the role of complement, particularly lectin pathway-mediated complement activation, in Stx-2-induced renal injury.

Radiocontrast Medium-Induced Kounis Syndrome in a Dialysis Patient: A Case Report.

Kounis syndrome is defined as the concurrence of acute coronary syndrome and a condition related to mast cell activation, including anaphylaxis and anaphylactoid. A 58-year-old male hemodialysis patient underwent enhanced computed tomography (CT) using the radiocontrast medium, iopamidol for investigation of a kidney tumor. Two minutes after the administration of iopamidol, he developed respiratory symptoms and chest pain. Five minutes after that, disturbed consciousness and low blood pressure were observed. On the other hand, he did not demonstrate urticaria and swelling of the skin. A 12-lead electrocardiogram (ECG) and echocardiogram suggested the presence of cardiac ischemia. Therefore, he was diagnosed with Kounis syndrome caused by radiocontrast media. Eighteen minutes after this, he received an intramuscular injection of adrenaline (0.3 mg), and his vital signs stabilized and his ECG, echocardiogram, and symptoms improved. Without undergoing emergency coronary angiography (CAG), he was hospitalized and closely monitored. The next day, his symptoms had not worsened, and he underwent hemodialysis at his local hospital. The allergen radiocontrast media could be injurious and not sufficiently excreted if administrated for patients on weekly hemodialysis with radiocontrast medium-induced Kounis syndrome manifesting; hence, indication for emergency CAG in radiocontrast medium-induced Kounis syndrome should be cautiously evaluated by close observation.

Association between loss of hypercoagulable phenotype, clinical features and complement pathway consumption in COVID-19.

Background: Coronavirus disease 2019 (COVID-19) features a hypercoagulable state, but therapeutic anticoagulation effectiveness varies with disease severity. We aimed to evaluate the dynamics of the coagulation profile and its association with COVID-19 severity, outcomes, and biomarker trajectories. Methods: This multicenter, prospective, observational study included patients with COVID-19 requiring respiratory support. Rotational thromboelastometry findings were evaluated for coagulation and fibrinolysis status. Hypercoagulable status was defined as supranormal range of maximum clot elasticity in an external pathway. Longitudinal laboratory parameters were collected to characterize the coagulation phenotype. Results: Of 166 patients, 90 (54%) were severely ill at inclusion (invasive mechanical ventilation, 84; extracorporeal membrane oxygenation, 6). Higher maximum elasticity (P=0.02) and lower maximum lysis in the external pathway (P=0.03) were observed in severely ill patients compared with the corresponding values in patients on non-invasive oxygen supplementation. Hypercoagulability components correlated with platelet and fibrinogen levels. Hypercoagulable phenotype was associated with favorable outcomes in severely ill patients, while normocoagulable phenotype was not (median time to recovery, 15 days vs. 27 days, P=0.002), but no significant association was observed in moderately ill patients. In patients with severe COVID-19, lower initial C3, minimum C3, CH50, and greater changes in CH50 were associated with the normocoagulable phenotype. Changes in complement components correlated with dynamics of coagulation markers, hematocrit, and alveolar injury markers. Conclusions: While hypercoagulable states become more evident with increasing severity of respiratory disease in patients with COVID-19, normocoagulable phenotype is associated with triggered by alternative pathway activation and poor outcomes.

Assessment of Critical Care Surge Capacity During the COVID-19 Pandemic in Japan.

Japan has the highest proportion of older adults worldwide but has fewer critical care beds than most high-income countries. Although the COVID-19 infection rate in Japan is low compared with Europe and the United States, by the end of 2020, several infected people died in ambulances because they could not find hospitals to accept them. Our study aimed to examine the Japanese healthcare system's capacity to accommodate critically ill COVID-19 patients during the pandemic. We created a model to estimate bed and staff capacity at 3 levels of pandemic response (conventional, contingency, and crisis), as defined by the US National Academy of Medicine, and the function of Japan's healthcare system at each level. We then compared our estimates of the number of COVID-19 patients requiring intensive care at peak times with the national health system capacity using expert panel data. Our findings suggest that Japan's healthcare system currently can accommodate only a limited number of critically ill COVID-19 patients. It could accommodate the surge of pandemic demands by converting nonintensive care unit beds to critical care beds and using nonintensive care unit staff for critical care. However, bed and staff capacity should not be expanded uniformly, so that the limited number of physicians and nurses are allocated efficiently and so staffing does not become the bottleneck of the expansion. Training and deploying physicians and nurses to provide immediate intensive care is essential. The key is to introduce and implement the concept and mechanism of tiered staffing in the Japanese healthcare system. More importantly, most intensive care facilities in Japanese hospitals are small-scaled and thinly distributed in each region. The government needs to introduce an efficient system for smooth dispatching of medical personnel among hospitals regardless of their founding institutions.

Relative platelet reductions provide better pathophysiologic signatures of coagulopathies in sepsis.

In sepsis-associated coagulopathies and disseminated intravascular coagulation, relative platelet reductions may reflect coagulopathy severity. However, limited evidence supports their clinical significance and most sepsis-associated coagulopathy criteria focus on the absolute platelet counts. To estimate the impact of relative platelet reductions and absolute platelet counts on sepsis outcomes. A multicenter retrospective observational study was performed using the eICU Collaborative Research Database, comprising 335 intensive care units (ICUs) in the United States. Patients with sepsis and an ICU stay > 2 days were included. Estimated effects of relative platelet reductions and absolute platelet counts on mortality and coagulopathy-related complications were evaluated. Overall, 26,176 patients were included. Multivariate mixed-effect logistic regression analysis revealed marked in-hospital mortality risk with larger platelet reductions between days one and two, independent from the resultant absolute platelet counts. The adjusted odds ratio (OR) [95% confidence intervals (CI)] for in-hospital mortality was 1.28[1.23-1.32], 1.86[1.75-1.97], 2.99[2.66-3.36], and 6.05[4.40-8.31] for 20-40%, 40-60%, 60-80%, and > 80% reductions, respectively, when compared with a < 20% decrease in platelets (P < 0.001 for each). In the multivariate logistic regression analysis, platelet reductions ≥ 11% and platelet counts ≤ 100,000/µL on day 2 were associated with high coagulopathy-related complications (OR [95%CI], 2.03 and 1.18; P < 0.001 and P < 0.001), while only platelet reduction was associated with thromboembolic complications (OR [95%CI], 1.43 [1.03-1.98], P < 0.001). The magnitude of platelet reductions represent mortality risk and provides a better signature of coagulopathies in sepsis; therefore, it is a plausible criterion for sepsis-associated coagulopathies.

Usefulness of Respiratory Mechanics and Laboratory Parameter Trends as Markers of Early Treatment Success in Mechanically Ventilated Severe Coronavirus Disease: A Single-Center Pilot Study.

Whether a patient with severe coronavirus disease (COVID-19) will be successfully liberated from mechanical ventilation (MV) early is important in the COVID-19 pandemic. This study aimed to characterize the time course of parameters and outcomes of severe COVID-19 in relation to the timing of liberation from MV. This retrospective, single-center, observational study was performed using data from mechanically ventilated COVID-19 patients admitted to the ICU between 1 March 2020 and 15 December 2020. Early liberation from ventilation (EL group) was defined as successful extubation within 10 days of MV. The trends of respiratory mechanics and laboratory data were visualized and compared between the EL and prolonged MV (PMV) groups using smoothing spline and linear mixed effect models. Of 52 admitted patients, 31 mechanically ventilated COVID-19 patients were included (EL group, 20 (69%); PMV group, 11 (31%)). The patients' median age was 71 years. While in-hospital mortality was low (6%), activities of daily living (ADL) at the time of hospital discharge were significantly impaired in the PMV group compared to the EL group (mean Barthel index (range): 30 (7.5-95) versus 2.5 (0-22.5), p = 0.048). The trends in respiratory compliance were different between patients in the EL and PMV groups. An increasing trend in the ventilatory ratio during MV until approximately 2 weeks was observed in both groups. The interaction between daily change and earlier liberation was significant in the trajectory of the thrombin-antithrombin complex, antithrombin 3, fibrinogen, C-reactive protein, lymphocyte, and positive end-expiratory pressure (PEEP) values. The indicator of physiological dead space increases during MV. The trajectory of markers of the hypercoagulation status, inflammation, and PEEP were significantly different depending on the timing of liberation from MV. These findings may provide insight into the pathophysiology of COVID-19 during treatment in the critical care setting.

Efficacy of favipiravir for an end stage renal disease patient on maintenance hemodialysis infected with novel coronavirus disease 2019.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) refers to infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, and has spread to pandemic levels since its inception in December 2019. While several risk factors for severe presentation have been identified, the clinical course for end-stage renal disease (ESRD) patients on maintenance hemodialysis with COVID-19 has been unclear. Previous studies have revealed that some antiviral agents may be effective against COVID-19 in the general population, but the pharmacokinetics and pharmacodynamics of these agents in ESRD patients remain under investigation. Favipiravir, an antiviral agent developed for treatment of influenza, is one candidate treatment for COVID-19, but suitable dosages for patients with renal insufficiency are unknown. Here we provide a first report on the efficacy of favipiravir in a patient with ESRD undergoing hemodialysis. CASE PRESENTATION: The case involved a 52-year-old woman with COVID-19 who had been undergoing maintenance hemodialysis three times a week for 3 years due to diabetic nephropathy. She had initially been treated with lopinavir/ritonavir and ciclesonide for 5 days, but developed severe pneumonia requiring invasive positive-pressure ventilation. Those antiviral agents were subsequently switched to favipiravir. She recovered gradually, and after 2 weeks was extubated once the viral load of SARS-CoV-2 fell below the limit of detection. Although concentrations of several biliary enzymes were elevated, no major adverse events were observed. CONCLUSION: Favipiravir may be an effective option for the treatment of COVID-19-infected patients with ESRD.

Clinical impact of visually assessed right ventricular dysfunction in patients with septic shock.

We retrospectively analyzed data from the Medical Information Mart for Intensive Care-III critical care database to determine whether visually-assessed right ventricular (RV) dysfunction was associated with clinical outcomes in septic shock patients. Associations between visually-assessed RV dysfunction by echocardiography and in-hospital mortality, lethal arrhythmia, and hemodynamic indicators to determine the prognostic value of RV dysfunction in patients with septic shock were analyzed. Propensity score analysis showed RV dysfunction was associated with increased risk of in-hospital death in patients with septic shock (adjusted odds ratio [OR] 2.15; 95% confidence interval [CI] 1.99-2.32; P < 0.001). In multivariate logistic regression analysis, RV dysfunction was associated with in-hospital death (OR 2.19; 95% CI 1.91-2.53; P < 0.001), lethal arrhythmia (OR 2.19; 95% CI 1.34-3.57; P < 0.001), and tendency for increased blood lactate levels (OR 1.31; 95% CI 1.14-1.50; P < 0.001) independent of left ventricular (LV) dysfunction. RV dysfunction was associated with lower cardiac output, pulmonary artery pressure index, and RV stroke work index. In patients with septic shock, visually-assessed RV dysfunction was associated with in-hospital mortality, lethal arrhythmia, and circulatory insufficiency independent of LV dysfunction. Visual assessment of RV dysfunction using echocardiography might help to identify the short-term prognosis of patients with septic shock by reflecting hemodynamic status.

A case of reexpansion pulmonary edema and acute pulmonary thromboembolism associated with diffuse large B-cell lymphoma treated with venovenous extracorporeal membrane oxygenation.

A 37-year-old man diagnosed with diffuse large B-cell lymphoma two weeks previously, visited our emergency department with sudden dyspnea. He had a severe respiratory failure with saturated percutaneous oxygen at 80% (room air). Chest radiography showed a large amount of left pleural effusion. After 1000 mL of the effusion was urgently drained, reexpansion pulmonary edema (RPE) occurred. Despite ventilator management, oxygenation did not improve and venovenous extracorporeal membrane oxygenation (VV-ECMO) was initiated in the intensive care unit. The next day, contrast-enhanced computed tomography showed a massive thrombus in the right pulmonary artery, at this point the presence of pulmonary thromboembolism (PTE) was revealed. Fortunately, the patient's condition gradually improved with anticoagulant therapy and VV-ECMO support. VV-ECMO was successfully discontinued on day 4, and chemotherapy was initiated on day 8. We speculated the following mechanism in this case: blood flow to the right lung significantly reduced due to acute massive PTE, and blood flow to the left lung correspondingly increased, which could have caused RPE in the left lung. Therefore, our observations suggest that drainage of pleural effusion when contralateral blood flow is impaired due to acute PTE may increase the risk of RPE. .

Reducing Aerosol Generation During Ventilator Weaning in a Coronavirus Disease 2019 Patient Using a Supraglottic Airway: A Case Report.

We report weaning from mechanical ventilation with no coughing in a patient with coronavirus disease 2019 (COVID-19). Substituting the endotracheal tube for a supraglottic airway (SGA), which is less stimulating to the trachea, can reduce coughing with weaning from mechanical ventilation and extubation. Personal protective equipment is in short supply worldwide. Reducing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is beneficial in terms of occupational health of health care workers.

Prognostic Impact of Parameters of Metabolic Acidosis in Critically Ill Children with Acute Kidney Injury: A Retrospective Observational Analysis Using the PIC Database.

Acute kidney injury (AKI) is a major complication of sepsis that induces acid-base imbalances. While creatinine levels are the only indicator for assessing the prognosis of AKI, prognostic importance of metabolic acidosis is unknown. We conducted a retrospective observational study by analyzing a large China-based pediatric critical care database from 2010 to 2018. Participants were critically ill children with AKI admitted to intensive care units (ICUs). The study included 1505 children admitted to ICUs with AKI, including 827 males and 678 females. The median age at ICU admission was 22 months (interquartile range 7-65). After a median follow-up of 10.87 days, 4.3% (65 patients) died. After adjusting for confounding factors, hyperlactatemia, low pH, and low bicarbonate levels were independently associated with 28-day mortality (respective odds ratio: 3.06, 2.77, 2.09; p values: <0.01, <0.01, <0.01). The infection had no interaction with the three parameters. The AKI stage negatively interacted with bicarbonate and pH but not lactate. The current study shows that among children with AKI, hyperlactatemia, low pH, and hypobicarbonatemia are associated with 28-day mortality.

Anesthetic and surgical management of tracheostomy in a patient with COVID-19.

OBJECTIVE: The ongoing pandemic coronavirus disease-2019 (COVID-19) infection causes severe respiratory dysfunction and has become an emergent issue for worldwide healthcare. Since COVID-19 spreads through contact and droplet infection routes, careful attention to infection control and surgical management is important to prevent cross-contamination of patients and medical staff. Tracheostomy is an effective method to treat severe respiratory dysfunction with prolonged respiratory management and should be performed as a high-risk procedure METHOD: The anesthetic and surgical considerations in this case involved difficult goals of the patient safety and the management of infection among health care workers. Our surgical procedure was developed based on the previous experiences of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). RESULTS: We described the management procedures for tracheostomy in a patient with COVID-19, including the anesthesia preparation, surgical procedures, required medical supplies (a N95 mask or powered air purifying respirator, goggles, face shield, cap, double gloves, and a water-resistant disposable gown), and appropriate consultation with an infection prevention team. CONCLUSION: Appropriate contact, airborne precautions, and sufficient use of muscle relaxants are essential for performing tracheostomy in a patient with COVID-19.

Independent lung ventilation with use of a double-lumen endotracheal tube for refractory hypoxemia and shock complicating severe unilateral pneumonia: A case report.

BACKGROUND: The indications for independent lung ventilation (ILV) in critical care settings have not been fully clarified, especially because extracorporeal membrane oxygenation (ECMO) is being used increasingly in cases of severe respiratory failure. CASE REPORT: A 90-year-old man presented with severe unilateral pneumonia, and despite conventional mechanical ventilation management with use of a single lumen endotracheal tube and high positive endo-expiratory pressure (PEEP), oxygenation and hemodynamics deteriorated. We then performed ILV using a double-lumen endotracheal tube (DLT) and two ventilators, each set at a different respiratory mode. With continuous administration of a neuromuscular blocking agent, the ventilator for the left lung (non-affected lung) was set to pressure-controlled ventilation (PCV) mode, whereas the ventilator for the right lung (affected lung) was set to bi-level mode, 1 breath/min, and high PEEP. ILV and the high PEEP applied to the affected lung prevented hyperinflation of the non-affected lung and increased pulmonary blood perfusion on the non-affected side. Thus, ILV immediately improved oxygenation and hemodynamics by correcting ventilation/perfusion mismatch. DISCUSSION: Although ECMO is a valid treatment option for patients with severe respiratory failure, it is highly invasive intervention. ILV performed with use of a DLT is less invasive and more useful than ECMO. Thus, ILV should be kept in mind as a treatment option, especially in cases of refractory respiratory failure and circulatory failure in which the pathophysiology of the left and right lungs differs markedly.

Relative bradycardia as a clinical feature in patients with coronavirus disease 2019 (COVID-19): A report of two cases.

We treated two patients with COVID-19 pneumonia requiring mechanical ventilation. Case 1 was a 73-year-old Japanese man. Computed tomography (CT) revealed ground-glass opacities in both lungs. He had severe respiratory failure with a partial pressure of oxygen in arterial blood/fraction of inspiratory oxygen ratio (P/F ratio) of 203. Electrocardiogram showed a heart rate (HR) of 56 beats/min, slight ST depression in leads II, III, and aVF, and mild saddle-back type ST elevation in leads V1 and V2. High-sensitivity cardiac troponin T (cTnT) level was slightly elevated. Despite a high fever and hypoxemia, his HR remained within 50-70 beats/min. Case 2 was a 52-year-old Japanese woman. CT revealed ground-glass opacities in the lower left lung. Electrocardiogram showed a HR of only 81 beats/min, despite a body temperature of 39.2 °C, slight ST depression in leads V4, V5, V6, and a prominent U wave in multiple leads. She had an elevated cTnT and a P/F ratio of 165. Despite a high fever and hypoxemia, her HR remained within 50-70 beats/min. Both patients had a poor compensatory increase in their HR, despite their critical status. Relative bradycardia could be a cardiovascular complication and is an important clinical finding in patients with COVID-19. .

Use of a Tracheal Tube as a Nasally Inserted Supraglottic Airway in a Case of Near-Fatal Airway Obstruction Caused by Epiglottitis.

Airway management is critical during near-fatal obstruction of the upper airway in epiglottitis; however, this is challenging because of the sitting posture and agitated mental status of the patient. Moreover, there is currently no established protocol for safe airway management in patients with epiglottitis. Here, we describe the use of a conventional tracheal tube as a nasolaryngeal airway to maintain airway patency at the site of airway narrowing in the supine position, which enabled alleviation of imminent airway obstruction in a patient with epiglottitis. For definitive airway establishment, tracheostomy was then safely performed in the supine position.

Noble gas binding to human serum albumin using docking simulation: nonimmobilizers and anesthetics bind to different sites.

BACKGROUND: Nonimmobilizers are structurally similar to anesthetics, but do not produce anesthesia at clinically relevant concentrations. Xenon, krypton, and argon are anesthetics, whereas neon and helium are nonimmobilizers. The structures of noble gases with anesthetics or nonimmobilizers are similar and their interactions are simple. Whether the binding site of anesthetics differs from that of nonimmobilizers has long been a question in molecular anesthesiology. METHODS: We investigated the binding sites and energies of anesthetic and nonimmobilizer noble gases in human serum albumin (HSA) because the 3D structure of HSA is well known and it has an anesthetic binding site. The computational docking simulation we used searches for binding sites and calculates the binding energy for small molecules and a template molecule. RESULTS: Xenon, krypton, and argon were found to bind to the enflurane binding site of HSA, whereas neon and helium were found to bind to sites different from the xenon binding site. Rare gas anesthetic binding was dominated by van der Waals energy, while nonimmobilizer binding was dominated by solvent-effect energy. Binding site preference was determined by the ratios of local binding energy (van der Waals energy) and nonspecific binding energy (solvent-effect energy) to the total binding energy. van der Waals energy dominance is necessary for anesthetic binding. CONCLUSIONS: This analysis of binding energy components provides a rationale for the binding site difference of anesthetics and nonimmobilizers, reveals the differences between the binding interactions of anesthetics and nonimmobilizers, may explain pharmacological differences between anesthetics and nonimmobilizers, and provide an understanding of anesthetic action at the atomic level.