Toshiaki Mochizuki

Prediction protocol for neurological outcome for survivors of out-of-hospital cardiac arrest treated with targeted temperature management ☆

AIM To identify patients who can obtain the full benefit from targeted temperature management (TTM) after out-of-hospital cardiac arrest. METHODS We performed a retrospective observational study of comatose patients treated with TTM after an out-of-hospital cardiac arrest from January 2006 to February 2011. Neurological outcome was evaluated with the Glasgow-Pittsburgh Cerebral Performance category (CPC) at discharge and predictors were determined. RESULTS Of 66 patients studied, 40 (60.6%) survived to neurologically intact discharge (CPC 1 or 2). According to multivariate analysis, predictors of good neurological outcome included arrest-to-first cardiopulmonary resuscitation attempt interval ≤5 min, ventricular fibrillation or ventricular tachycardia in the first monitored rhythm, absence of re-arrest before leaving the emergency department, arrest-to-return of spontaneous circulation interval ≤30 min and recovery of pupillary light reflex, which were identifiable in the emergency department. Based on this analysis, we developed a seven-point score (5-R score). If the score was ≥5, it predicted good neurological outcome with a sensitivity of 82.5% (95% confidence interval [CI], 67.2-92.7%) and specificity of 92.3% (95% CI, 74.9-99.1%). The negative predictive value of a score ≥4 was 100% (95% CI, 81.5-100%). Our prediction model was validated internally by a bootstrapping technique. CONCLUSIONS The prediction protocol using the 5-R score was associated with good neurological outcome of patients treated with TTM. Therefore, it could be helpful in clinical decision making on whether to initiate cooling.

Regional cerebral oxygen saturation monitoring for predicting interventional outcomes in patients following out-of-hospital cardiac arrest of presumed cardiac cause: A prospective, observational, multicentre study

AIM This study investigated the value of regional cerebral oxygen saturation (rSO2) monitoring upon arrival at the hospital for predicting post-cardiac arrest intervention outcomes. METHODS We enrolled 1195 patients with out-of-hospital cardiac arrest of presumed cardiac cause from the Japan-Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry. The primary endpoint was a good neurologic outcome (cerebral performance categories 1 or 2 [CPC1/2]) 90 days post-event. RESULTS A total of 68 patients (6%) had good neurologic outcomes. We found a mean rSO2 of 21%±13%. A receiver operating characteristic curve analysis indicated an optimal rSO2 cut-off of ≥40% for good neurologic outcomes (area under the curve 0.92, sensitivity 0.81, specificity 0.96). Good neurologic outcomes were observed in 53% (55/103) and 1% (13/1092) of patients with high (≥40%) and low (<40%) rSO2, respectively. Even without return of spontaneous circulation (ROSC) upon arrival at the hospital, 30% (9/30) of patients with high rSO2 had good neurologic outcomes. Furthermore, 16 patients demonstrating ROSC upon arrival at the hospital and low rSO2 had poor neurologic outcomes. Multivariate analyses indicated that high rSO2 was independently associated with good neurologic outcomes (odds ratio=14.07, P<0.001). Patients with high rSO2 showed favourable neurologic prognoses if they had undergone therapeutic hypothermia or coronary angiography (CPC1/2, 69% [54/78]). However, 24% (25/103) of those with high rSO2 did not undergo these procedures and exhibited unfavourable neurologic prognoses (CPC1/2, 4% [1/25]). CONCLUSION rSO2 is a good indicator of 90-day neurologic outcomes for post-cardiac arrest intervention patients.

Acute group poisoning by titanium dioxide: inhalation exposure may cause metal fume fever

A large quantity of white gas containing titanium dioxide and hydrogen chloride was generated unexpectedly during an experiment in a chemical laboratory. Fourteen students and staff complained of nausea, dyspnea, or respiratory irritation immediately after inhaling the gas. On arrival at Saint Lukes International Hospital, more than half of the patients presented with low-grade fever. Symptoms spontaneously resolved soon after admission, although the low-grade fever persisted until the following morning. Low-grade fever after inhalation exposure is not explicable by hydrogen chloride inhalation and therefore appeared to be caused by titanium dioxide inhalation, manifesting as metal fume fever. Titanium dioxide is thought to have no remarkable human toxicity and is considered to be safe clinically. To our knowledge, this is the first report of titanium dioxide inhalation as the potential cause of metal fume fever in humans. Correlations between the degree of fever and quantity and concentration of inhaled titanium dioxide remain to be determined.

Anisakiasis presenting to the ED: clinical manifestations, time course, hematologic tests, computed tomographic findings, and treatment

BACKGROUND The prevalence of anisakiasis is rare in the United States and Europe compared with that in Japan, with few reports of its presentation in the emergency department (ED). This study describes the clinical, hematologic, computed tomographic (CT) characteristics, and treatment in gastric and small intestinal anisakiasis patients in the ED. METHODS We retrospectively reviewed the data of 83 consecutive anisakiasis presentations in our ED between 2003 and 2012. Gastric anisakiasis was endoscopically diagnosed with the Anisakis polypide. Small intestinal anisakiasis was diagnosed based on both hematologic (Anisakis antibody) and CT findings. RESULTS Of the 83 cases, 39 had gastric anisakiasis and 44 had small intestinal anisakiasis based on our diagnostic criteria. Although all patients had abdominal pain, the gastric anisakiasis group developed symptoms significantly earlier (peaking within 6 hours) than the small intestinal anisakiasis group (peaking within 48 hours), and fewer patients with gastric anisakiasis needed admission therapy (5% vs 57%, P<.01). All patients in the gastric and 40 (91%) in the small intestinal anisakiasis group had a history of raw seafood ingestion. Computed tomographic findings revealed edematous wall thickening in all patients, and ascites and phlegmon of the mesenteric fat were more frequently observed in the small intestinal anisakiasis group. CONCLUSIONS In the ED, early and accurate diagnosis of anisakiasis is important to treat and explain to the patient, and diagnosis can be facilitated by a history of raw seafood ingestion, evaluation of the time-to-symptom development, and classic CT findings.

Hypocapnia prolongs bradycardia induced by bupivacaine or levobupivacaine in isolated rat hearts

Purpose: Systemic alkalinization is recommended for resuscitation from local anesthetic-induced cardiotoxicity. It has been suggested that inducing hypocapnic alkalosis, prior to exposure to toxic concentrations of local anesthetics, may minimize cardiotoxicity. However, it remains unclear whether inducing severe hypocapnic alkalosis after administration of local anesthetics will minimize the duration of bradycardia. We used isolated rat hearts to investigate the effects of hypocapnic alkalosis on heart rate (HR) recovery from bupivacaine or levobupivacaine-induced bradycardia.Methods: We measured the time required for the HR in 24 isolated rat hearts, respectively, to attain 90% of the baseline HR (recovery time) following bradycardia induced by 1µg·mL−1 and 10µg·mL−1 concentrations of either bupivacaine or levobupivacaine. Normal pH perfusate (bupivacaine or levobupivacaine with normal pH washout groups) or severe hypocapnic alkalosis perfusate (bupivacaine or levobupivacaine with hypocapnic alkalosis washout groups) were reperfused after exposure to the local anesthetics.Results: Severe hypocapnic alkalosis prolonged the recovery time from 273 ± 122 sec, at the 1µg·mL−1 bupivacaine concentration with normal pH washout, to 1203 ± 540 sec, in the bupivacaine with hypocapnic alkalosis washout (P=0.029). Severe hypocapnic alkalosis also prolonged the recovery time from 1 153 ± 644 sec, at a 10µg·mL−1 bupivacaine concentration in the normal pH washout group, to 2065 ±617 sec, in the bupivacaine with hypocapnic alkalosis washout group (P=0.032). With levobupivacaine 10µg·mL−1 in the normal pH washout group, HR recovery time increased from 863 ± 186 sec to 1565 ± 567 sec, compared to the hypocapnic alkalosis washout group (P=0.045).Conclusions: Severe hypocapnic alkalosis prolonged the recovery time from bupivacaine or levobupivacaine-induced bradycardia in isolated rat hearts. When bradycardia occurs after intravascular bupivacaine or levobupivacaine administration, maintenance of normocapnia may minimize the duration of bradycardia.RésuméObjectif: L’alcalinisation systémique est recommandée pour la réanimation dans les cas de cardiotoxicité provoquée par un anesthésique local. Il a été suggéré que l’induction d’une alcalose hypocapnique avant l’exposition à des concentrations toxiques d’anesthésiques locaux pourrait minimiser la cardiotoxicité. Cependant, nous ne savons pas si l’induction d’une alcalose hypocapnique grave après l’administration d’anesthésiques locaux minimise la durée de la bradycardie. Nous avons utilisé des cœurs isolés de rats pour analyser les effets de l’alcalose hypocapnique sur le retour à une fréquence cardiaque (FC) normale à la suite d’une bradycardie provoquée par la bupivacaïne ou la lévobupivacaine.Méthode: Nous avons mesuré le temps requis pour que la FC de 24 cœurs isolés de rats atteigne 90 % de la FC de base (temps de récupération) après une bradycardie provoquée par des concentrations de 1 µg·mL−1 et 10 µg·mL−1 de bupivacaïne ou de lévobupivacaïne. Un perfusat au pH normal (groupes bupivacaïne ou lévobupivacaïne avec solution de rinçage à pH normal) ou un perfusat d’alcalose hypocapnique sévère (groupes bupivacaïne ou lévobupivacaïne avec solution de rinçage alcaline hypocapnique) a été reperfusé après que les cœurs ont été exposés aux anesthésiques locaux.Résultats: L’alcalose hypocapnique grave a prolongé le temps de récupération de 273 ± 122 sec, à la concentration de bupivacaïne del µg·mL−1 avec la solution de rinçage à pH normal, à 1203 ± 540 sec, dans le groupe de bupivacaïne avec la solution de rinçage alcaline hypocapnique (P=0,029). L’alcalose hypocapnique grave a également prolongé le temps de récupération de 1153 ± 644 sec, à une concentration de bupivacaïne 10 µg·mL−1, à 2065 ±617 sec dans le groupe de bupivacaïne avec solution de rinçage alcaline hypocapnique (P=0,032). Avec de la lévobupivacaïne 10 µg·mL−1 dans le groupe à la solution de rinçage au pH normal, le temps de récupération de la fréquence cardiaque a augmenté de 863 ± 186 sec à 1565 ± 567 sec, comparativement au groupe avec solution de lavage alcaline hypocapnique (P=0,045).Conclusion: L’alcalose hypocapnique a prolongé le temps de récupération après une bradycardie provoquée par la bupivacaïne ou la lévobupivacaïne dans des cœurs isolés de rats. Lorsque la bradycardie survient après l’administration intravasculaire de bupivacaïne ou de lévobupivacaïne, le maintien de la normocapnie pourrait minimiser la durée de la bradycardie.

Nitric oxide donor, NOC7, reveals biphasic effect on contractile force of isolated rat heart after global ischemia

PurposeOur purpose was to investigate whether the NO donor, 3-(2-hydroxy-1-methyl-2-nitroso-hydrazino)-N-methyl-1-propanamine (NOC7), restored cardiac function following global ischemia in an isolated rat heart model and whether intracellular messengers were involved in its effect.MethodsIsolated rat hearts (n = 36) were randomly divided into six groups. The sham control group was perfused with modified Krebs-Henseleit bicarbonate buffer (KHB) alone. The ischemic control group and the NOC7 groups were subjected to 35 min of global ischemia, followed by 30 min of reperfusion with KHB alone, or reperfusion with KHB including NOC7 at 0.2, 2, 20, or 200 μM, respectively. Left ventricular developed pressure (LVDP), the maximum and the minimal rate of rise in LVP (±dP/dt), and coronary flow were measured continuously. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were measured in myocardium homogenate, using enzyme immunoassay (EIA) methods.ResultsNOC7 at 2 and 20 μM rescued myocardial performance (LVDP, 111.9 ± 10.5% and 124.3 ± 12.5% of baseline, respectively; P < 0.05 vs ischemic control) at 30 min after reperfusion. However, NOC7 at 200 μM reduced the LVDP to 55.3 ± 6.0% of baseline. Coronary flows remain unchanged. The cAMP levels increased significantly from 0.83 ± 0.44 pmol·mg−1 protein in the ischemic control group to 1.79 ± 0.39, 1.86 ± 0.25, and 2.63 ± 0.24 pmol·mg−1 protein, in the groups with NOC7 at 2, 20, and 200 μM, respectively (P < 0.05). The cGMP level increased from 1.49 ± 0.61 pmol·mg−1 protein in the ischemic control group to 3.92 ± 0.66 pmol·mg−1 protein in the group with NOC7 at 200 μM alone (P < 0.05).ConclusionNOC7 appeared to exert a biphasic effect on the contractile force of the isolated rat heart after 35-min global ischemia. The balance between intracellular cAMP and cGMP levels seemed to be involved in its mechanism.

Quality of cardiopulmonary resuscitation affects cardioprotection by induced hypothermia at 34 °C against ischemia/reperfusion injury in a rat isolated heart model.

ABSTRACT In this study, we aimed to compare the effects of low- and high-quality cardiopulmonary resuscitation (CPR) on cardioprotection by induced hypothermia (IH) at 34°C and examine whether extracellular signal–regulated kinase or endothelial nitric oxide synthase mediates this cardioprotection. Left ventricle infarct sizes were evaluated in six groups of rat hearts (n = 6) following Langendorff perfusion and triphenyltetrazolium chloride staining. Controls underwent 30 min of global ischemia at 37°C, followed by 10 min of simulated low- or high-quality CPR reperfusion and 90 min of reperfusion at 75 mmHg. The IH groups underwent IH at 34°C during reperfusion. The U0126 group received U0126 (60 &mgr;M)—an extracellular signal–regulated kinase inhibitor—during reperfusion at 34°C. The L-NIO (N5-(1-iminoethyl)-L-ornithine dihydrochloride) group received L-NIO (2 &mgr;M)—an endothelial nitric oxide synthase inhibitor—5 min before global ischemia at 37°C to the end of reperfusion at 34°C. Infarct size did not significantly differ between the control and IH groups receiving low-quality CPR. However, IH with high-quality CPR reduced the infarct size from 47.2% ± 10.2% to 26.0% ± 9.4% (P = 0.005). U0126 reversed the IH-induced cardioprotection (45.9% ± 9.4%, P = 0.010), whereas L-NIO had no significant effect. Cardiopulmonary resuscitation quality affects IH-induced cardioprotection. Extracellular signal–regulated kinase may mediate IH-induced cardioprotection.

Reliability of anion gap calculated from data obtained using a blood gas analyzer: is the probability of error predictable?

BACKGROUND Anion gap (AG) is a useful index for assessing the clinical condition of critically ill patients especially in intoxication. Recently, AG can be obtained easily using a blood gas analyzer (BGA); however, its reliability requires validation. METHODS We enrolled patients who simultaneously underwent blood gas analysis and blood test in the central hospital laboratory and patients who visited the emergency department of our hospital from January 1, 2004, to December 31, 2007. The deviation of AG calculated using the BGA and that calculated by the central hospital laboratory were extracted. From the data obtained using the BGA, the independent risk factor causing a significant error in AG was statistically analyzed. RESULTS A total of 2922 patients were enrolled, of which 339 were defined as the significant error group. Male sex, abnormal Hco(3)(-), abnormal lactate, abnormal K, abnormal Cl, and abnormal Na were the independent risk factors producing the significant error. The results indicate that regardless of whether the original electrolyte data of the patients are abnormal, when the electrolyte measurement results obtained using the BGA are abnormal, the calculated AG might show a significant error. In addition, the fact that lactate was determined as a risk factor indicates that AG might be more useful in patients who have intoxication than in those under an unstable state in terms of vital signs. CONCLUSION When risk factors are present, the medical condition of a patient should be reevaluated by comparing results without heavily relying on the AG obtained by a BGA.

Crowned dens syndrome

Dear Editor, A 90-year-old man visited our emergency department owing to neck pain and occipital headache. The pain occurred suddenly a few days previous, and had become gradually worse. He had a history of cerebral infarction, dementia, and cholelithiasis, but was not on any medication. The patient’s vital signs were stable excluding a body temperature of 37.5°C. Physical examination showed the reduction of passive cervical spine movements with posterior neck pain and occipital headache. Rotation, extension, and flexion in the neck were all limited. However, there was no tenderness in the nape of the neck. In terms of neurological findings, overall cranial nerve, motor, and sensory nervous systems were intact. In laboratory data, the value of the C-responsive protein was 4.34 mg/dL (normal range, 0.0–0.1 mg/dL); all other findings were unremarkable. Computed tomography (CT) of the neck showed crown-shaped calcium deposits surrounding the odontoid process (Fig. 1A, arrows), and dotted calcifications of the transverse ligament of the atlas (Fig. 1B, arrows).There were no other lesions causative of pain in brain or spine. By integrating the results, we diagnosed crowned dens syndrome (CDS). The chief complaint of patients of CDS is neck pain, due to calcification deposition around the odontoid process. The cause of CDS is thought to be the microcrystalline deposition, most often calcium pyrophosphate dihydrate crystals and/or hydroxyapatite crystals, in the transverse ligament of the atlas around the odontoid process. However, the pathophysiologic process has not been completely proven. Clinicians could confuse the differential diagnosis and misdiagnose CDS as meningitis, polymyalgia rheumatica, or dissecting aneurysm of the vertebral and basilar artery. In particular, meningitis must be considered first in the differential diagnosis because the triad of fever, headache, and neck stiffness due to meningitis are very similar to the symptoms of CDS. Using CT scans, CDS is identified in up to 5% of the patients over the age of 70 years who present to hospital with the chief symptom of neck pain. Therefore, it is not a rare entity but becoming unclear using plain radiography for the diagnosis because of improper images. Computed tomography is the gold standard for detecting calcification in transverse, apical, and alar ligaments. However, when the CT scan is carried out a long time after the onset of symptoms, calcification around the odontoid process may not be detected as it may have been absorbed. Non-steroidal anti-inflammatory drugs (NSAIDs) have been commonly used as first-line therapy for CDS. In cases without improvement using NSAIDs alone, treatment with moderate dosage of corticosteroids is recommended. In our case, NSAID therapy alleviated the patient’s symptoms completely. Taiki Yamada, Takeji Saitoh, Hironao Hozumi, Yoshiaki Takahashi, Masashi Nozawa, Toshiaki Mochizuki, and Atsuto Yoshino Department of Emergency and Disaster Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

The potential of leg-foot chest compression as an alternative to conventional hands-on compression during cardiopulmonary resuscitation:

Background: Conventional hands-on chest compression, in cardiopulmonary resuscitation, is often inadequate, especially when the rescuers are weak or have a small physique. Objectives: This study aimed to investigate the potential of leg-foot chest compression, with and without a footstool, during cardiopulmonary resuscitation. Methods and Results: We prospectively enrolled 21 medical workers competent in basic life support. They performed cardiopulmonary resuscitation on a manikin for 2 min using conventional hands-on compression (HO), leg-foot compression (LF), and leg-foot compression with a footstool (LF + FS). We analyzed the compression depths, changes in the rescuers’ vital signs, and the modified Borg scale scores after the trials. The compression depth did not differ between the cases using HO and LF. In the case of LF + FS, compression depths ⩾5 cm were more frequently observed (median, inter-quartile range: 93%, 81%–100%) than in HO (9%, 0%–57%, p < 0.01) and LF (28%, 11%–47%, p < 0.01). The increase in the heart rate or modified Borg scale scores, after the trials, did not differ between the HO and LF group; however, the values were the lowest in the case of LF + FS (49 ± 18 beats/min and 5 (4–7) in HO, 46 ± 18 and 6 (5–7) in LF, and 32 ± 11 and 2 (1–3) in LF + FS, respectively, p < 0.01). However, the increase in blood pressure, SpO2, and respiratory rate were not different among each group. The increases in the heart rate and modified Borg scale scores negatively were correlated with the rescuers’ body size, in the case of HO and LF, but not LF + FS. Conclusion: LF can be used as an alternative to HO, when adequate HO is difficult. LF + FS could be used when rescuers are weak or have a small physique and when the victims are bigger than the rescuers.