Tomoyoshi Tamura

Early Lactate Clearance Is Associated With Improved Outcomes in Patients With Postcardiac Arrest Syndrome: A Prospective, Multicenter Observational Study (sos-kanto 2012 Study)

Objectives: To determine whether early lactate reduction is associated with improved survival and good neurologic outcome in patients with out-of-hospital cardiac arrest. Design: Ad hoc data analysis of a prospective, multicenter observational study. Setting: Out-of-hospital cardiac arrest patients at 67 emergency hospitals in Kanto, Japan between January 2012 and March 2013. Patients: Adult patients with out-of-hospital cardiac arrest admitted to the hospital after successful resuscitation were identified. Interventions: Blood lactate concentrations were measured at hospital admission and 6 h after hospital admission. Early lactate clearance was defined as the percent change in lactate level 6 h after a baseline measurement. Measurements and Main Results: The 543 patients (mean age, 65 ± 16 yr; 72.6% male) had a mean lactate clearance of 42.4% ± 53.7%. Overall 30-day survival and good neurologic outcome were 47.1% and 27.4%, respectively. The survival proportion increased with increasing lactate clearance (quartile 1, 29.4%; quartile 2, 42.6%; quartile 3, 51.5%; quartile 4, 65.2%; p < 0.001). Multivariate logistic regression analysis showed that lactate clearance quartile was an independent predictor of the 30-day survival and good neurologic outcome. In the Cox proportional hazards model, the frequency of mortality during 30 days was significantly higher for patients with lactate clearance in quartile 1 (hazard ratio, 3.12; 95% CI, 2.14–4.53), quartile 2 (hazard ratio, 2.13; 95% CI, 1.46–3.11), and quartile 3 (hazard ratio, 1.49; 95% CI, 1.01–2.19) than those with lactate clearance in quartile 4. Furthermore, multivariate logistic regression analysis revealed that lactate clearance was a significant predictor of good neurologic outcome at 30 days after hospital admission. Conclusions: Effective lactate reduction over the first 6 hours of postcardiac arrest care was associated with survival and good neurologic outcome independently of the initial lactate level.

Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome – First-in-Human Pilot Study –

BACKGROUND Hydrogen gas inhalation (HI) ameliorates cerebral and cardiac dysfunction in animal models of post-cardiac arrest syndrome (PCAS). HI for human patients with PCAS has never been studied. METHODSANDRESULTS Between January 2014 and January 2015, 21 of 107 patients with out-of-hospital cardiac arrest achieved spontaneous return of circulation. After excluding 16 patients with specific criteria, 5 patients underwent HI together with target temperature management (TTM). No undesirable effects attributable to HI were observed and 4 patients survived 90 days with a favorable neurological outcome. CONCLUSIONS HI in combination with TTM is a feasible therapy for patients with PCAS. (Circ J 2016; 80: 1870-1873).

The Effects of Hydrogen Gas Inhalation on Adverse Left Ventricular Remodeling After Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction ― First Pilot Study in Humans ―

BACKGROUND Hydrogen gas inhalation (HI) reduced infarct size and mitigated adverse left ventricular (LV) remodeling in a rat model of acute myocardial infarction (AMI). We designed a prospective, open-label, rater-blinded clinical pilot study in patients experiencing ST-elevated MI (STEMI).Methods and Results:The 20 patients with an initial diagnosis of STEMI were assigned to either an HI group (1.3% H2with 26% oxygen) or a control group (26% oxygen). There were no HI-related severe adverse events. In the full analysis set, the cardiac salvage index as evaluated using cardiac magnetic resonance imaging at 7 days after primary percutaneous coronary intervention (PCI), showed no significant between-group difference (HI: 50.0±24.3%; control: 60.1±20.1%; P=0.43). However, the improvement from day 7 in the HI group was numerically greater than that in the control group in some of the surrogate outcomes at 6-month follow-up, including the LV stroke volume index (HI: 9.2±7.1 mL/m2; control: -1.4±7.2 mL/m2; P=0.03) and the LV ejection fraction (HI: 11.0%±9.3%; control: 1.7%±8.3%; P=0.11). CONCLUSIONS The first clinical study has shown that HI during PCI is feasible and safe and may also promote LV reverse remodeling at 6 months after STEMI. The study was not powered to test efficacy and a further large-scale trial is warranted. (Clinical trials registration: UMIN00006825).

Quantitative assessment of pupillary light reflex for early prediction of outcomes after out-of-hospital cardiac arrest: A multicentre prospective observational study

AIM To clarify whether quantitative assessment of pupillary light reflexes (PLR) can predict the outcome of post-cardiac arrest (CA) patients during the first 72 h after the return of spontaneous circulation (ROSC). METHODS Fifty adults resuscitated after non-traumatic out-of-hospital CA (OHCA) (mean age 64.1 years old, 36 males) were enrolled in four emergency hospitals. PLR was sequentially measured at 0, 6, 12, 24, 48, and 72 h after ROSC by an automated portable infrared pupillometry. PLR values for each time point were compared between both survivors and non-survivors, and patients with either favourable (Cerebral Performance Category (CPC) 1 or 2) or unfavourable neurological outcomes. RESULTS Twenty-three patients survived for 90 days after CA, and 13 patients achieved favourable neurological outcomes. The PLR values of the survivors and patients with favourable neurological outcomes were consistently greater than those of non-survivors (P < 0.001) and those with unfavourable neurological outcomes (P < 0.001), respectively. The change in PLR over time was not statistically different between the outcome groups. The 0-hour PLR best predicted both 90-day survival (AUC = 0.82, cutoff 3%, sensitivity 0.87, specificity 0.80) and favourable neurological outcomes (AUC = 0.84, cutoff 6%, sensitivity 0.92, specificity 0.74). No patient with a 6-hour PLR less than 3% survived for 90 days after CA. CONCLUSIONS Quantitatively measured PLR was consistently greater in survivors and patients with favourable neurological outcomes during the 72 h after ROSC. Quantitative assessment of PLR at as early as 0 h has a potential role for prognostication in post-CA patients.

Hydrogen gas inhalation inhibits progression to the "irreversible" stage of shock after severe hemorrhage in rats

BACKGROUND Mortality of hemorrhagic shock primarily depends on whether or not the patients can endure the loss of circulating volume until radical treatment is applied. We investigated whether hydrogen (H2) gas inhalation would influence the tolerance to hemorrhagic shock and improve survival. METHODS Hemorrhagic shock was achieved by withdrawing blood until the mean arterial blood pressure reached 30–35 mm Hg. After 60 minutes of shock, the rats were resuscitated with a volume of normal saline equal to four times the volume of shed blood. The rats were assigned to either the H2 gas (1.3% H2, 26% O2, 72.7% N2)-treated group or the control gas (26% O2, 74% N2)-treated group. Inhalation of the specified gas mixture began at the initiation of blood withdrawal and continued for 2 hours after fluid resuscitation. RESULTS The survival rate at 6 hours after fluid resuscitation was 80% in H2 gas-treated rats and 30% in control gas-treated rats (p < 0.05). The volume of blood that was removed through a catheter to induce shock was significantly larger in the H2 gas-treated rats than in the control rats. Despite losing more blood, the increase in serum potassium levels was suppressed in the H2 gas-treated rats after 60 minutes of shock. Fluid resuscitation completely restored blood pressure in the H2 gas-treated rats, whereas it failed to fully restore the blood pressure in the control gas-treated rats. At 2 hours after fluid resuscitation, blood pressure remained in the normal range and metabolic acidosis was well compensated in the H2 gas-treated rats, whereas we observed decreased blood pressure and uncompensated metabolic acidosis and hyperkalemia in the surviving control gas-treated rats. CONCLUSIONS H2 gas inhalation delays the progression to irreversible shock. Clinically, H2 gas inhalation is expected to stabilize the subject until curative treatment can be performed, thereby increasing the probability of survival after hemorrhagic shock.

Renal Function and Outcome of Out-of-Hospital Cardiac Arrest ― Multicenter Prospective Study (SOS-KANTO 2012 Study) ―

BACKGROUND Renal dysfunction is associated with increased cardiovascular-related mortality, but its impact on outcome of out-of-hospital cardiac arrest (OHCA) remains unclear. We assessed whether post-OHCA outcome correlated with renal function early after OHCA. Methods and Results: Of the 16,452 registered patients in the SOS-KANTO 2012 Study, 5,112 cardiogenic OHCA adults with creatinine measurement (mean age, 72 years; male, 64%) were examined. First-obtained creatinine was used to assess eGFR. Associations between eGFR groups, ≥60 (n=997), 45-59 (n=1,311), 30-44 (n=1,441), and <30 mL/min/1.73 m2(n=1,363), and 3-month survival and neurological outcomes were examined. Favorable neurological outcome was defined as cerebral performance categories 1 or 2. Survival rate (15.1%, 9.7%, 3.9%, and 2.9%; P<0.001) and proportion of favorable neurological outcome (12.3%, 7.4%, 2.6%, and 2.2%; P<0.001) were determined for eGFR groups ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. The survival rate decreased with eGFR (<60 mL/min/1.73 m2), and survival adjusted OR were 0.74 (95% CI: 0.54-1.03), 0.42 (95% CI: 0.28-0.62), and 0.43 (95% CI: 0.28-0.68) for eGFR 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. The adjusted OR for favorable neurological outcome also decreased with eGFR: 0.74 (95% CI: 0.52-1.06), 0.40 (95% CI: 0.25-0.64), and 0.48 (95% CI: 0.29-0.81), respectively. CONCLUSIONS An independent and graded association was observed between decreased eGFR and 3-month survival and proportion of favorable neurological outcome in cardiogenic OHCA patients.

Promising novel therapy with hydrogen gas for emergency and critical care medicine

It has been reported that hydrogen gas exerts a therapeutic effect in a wide range of disease conditions, from acute illness such as ischemia–reperfusion injury, shock, and damage healing to chronic illness such as metabolic syndrome, rheumatoid arthritis, and neurodegenerative diseases. Antioxidant and anti‐inflammatory properties of hydrogen gas have been proposed, but the molecular target of hydrogen gas has not been identified. We established the Center for Molecular Hydrogen Medicine to promote non‐clinical and clinical research on the medical use of hydrogen gas through industry–university collaboration and to obtain regulatory approval of hydrogen gas and hydrogen medical devices (http://www.karc.keio.ac.jp/center/center-55.html). Studies undertaken by the Center have suggested possible therapeutic effects of hydrogen gas in relation to various aspects of emergency and critical care medicine, including acute myocardial infarction, cardiopulmonary arrest syndrome, contrast‐induced acute kidney injury, and hemorrhagic shock.