Relationship between the administration of nicardipine hydrochloride and the development of delirium in patients on mechanical ventilation.

A history of hypertension is a known risk factor for delirium in patients in intensive care units, but the effect of antihypertensive agents on delirium development is unclear. Nicardipine, a calcium channel blocker, is widely used in ICU as a treatment agent for hypertensive emergency. This study investigated the relationship between the administration of nicardipine hydrochloride and delirium development in patients under mechanical ventilation. We conducted a medical chart review of 103 patients, who were divided into two groups according to the use of nicardipine hydrochloride. The prevalence of delirium was compared with respect to factors such as age, sex, laboratory data, and medical history, by multivariate analysis. 21 patients (20.4 %) were treated with nicardipine hydrochloride in 103 patients. The treatment and non-treatment groups differed significantly in age (72 vs. 65 years) and history of high blood pressure (57% vs. 11%). Multivariate analysis revealed that patients in the treatment group developed delirium significantly less often than those in the non-treatment group (19% vs. 48%). These results suggested that treatment of high blood pressure with nicardipine hydrochloride is a possible method for preventing the development of delirium.

Improved survival with an innovative approach to the treatment of severely burned patients: development of a burn treatment manual.

The management of severely burned patients remains a major issue worldwide as indicated by the high incidence of permanent debilitating complications and poor survival rates. In April 2012, the Advanced Emergency & Critical Care Medical Center of the Okayama University Hospital began implementing guidelines for severely burned patients, distributed as a standard burn treatment manual. The protocol, developed in-house, was validated by comparing the outcomes of patients with severe extensive burns (SEB) treated before and after implementation of these new guidelines at this institution. The patients included in this study had a burn index (BI) ≥30 or a prognostic burn index (PBI = BI + patient's age) ≥100. The survival rate of the patients with BI ≥30 was 65.2% with the traditional treatment and 100% with the new guidelines. Likewise, the survival rate of the patients with PBI ≥100 was 61.1% with the traditional treatment compared to 100% with the new guidelines. Together, these data demonstrate that the new treatment guidelines dramatically improved the treatment outcome and survival of SEB patients.

La prise en charge des patients gravement brûlés est toujours un problème majeur dans le monde, avec une mortalité élevée et de lourdes séquelles chez les survivants. En Avril 2012, le Centre de l'Hôpital de l'Université d'Okayama a commencé à distribuer un manuel pour le traitement des patients gravement brûlés. Notre protocole a été validé en comparant les résultats des patients souffrant de brûlures étendues traités avant et après la mise en oeuvre de ces nouvelles lignes directrices. Les patients inclus dans cette étude avaient une surface brûlée (SB) ≥30% ou un index de Baux (IBx= SB + âge du patient) ≥100. Le taux de survie chez les patients atteints sur ≥30% SB était de 65.2% avant et 100% après. Le taux de survie chez les patients avec un IBx ≥100 était de 61.1% avant et 100% après. Ces données démontrent que les nouvelles lignes directrices de traitement ont amélioré considérablement la survie chez ces patients.

Extracorporeal membrane oxygenation following pediatric cardiac surgery: development and outcomes from a single-center experience.

Extracorporeal membrane oxygenation (ECMO) has emerged as an effective mechanical support following cardiac surgery with respiratory and cardiac failure. However, there are no clear indications for ECMO use after pediatric cardiac surgery. We retrospectively reviewed medical records of 76 pediatric patients [mean age, 10.8 months (0-86); mean weight, 5.16 kg (1.16-16.5)] with congenital heart disease who received ECMO following cardiac surgery between January 1997 and October 2010. Forty-five patients were treated with an aggressive ECMO approach (aggressive ECMO group, April 2005-October 2010) and 31 with a delayed ECMO approach (delayed ECMO group, January 1997-March 2005). Demographics, diagnosis, operative variables, ECMO indication, and duration of survivors and non-survivors were compared. Thirty-four patients (75.5%) were successfully weaned from ECMO in the aggressive ECMO group and 26 (57.7%) were discharged. Conversely, eight patients (25.8%) were successfully weaned from ECMO in the delayed ECMO group and two (6.5%) were discharged. Forty-five patients with shunted single ventricle physiology (aggressive: 29 patients, delayed: 16 patients) received ECMO, but only 15 (33.3%) survived and were discharged. The survival rate of the aggressive ECMO group was significantly better when compared with the delayed ECMO group (p<0.01). Also, ECMO duration was significantly shorter among the aggressive ECMO group survivors (96.5 ± 62.9 h, p<0.01). Thus, the aggressive ECMO approach is a superior strategy compared to the delayed ECMO approach in pediatric cardiac patients. The aggressive ECMO approach improved our outcomes of neonatal and pediatric ECMO.

Confocal imaging analysis of ATP-induced Ca2+ response in individual endothelial cells of the artery in situ.

The mechanisms for mobilization of intracellular free Ca2+ have been studied in various types of isolated and cultured cells, but little is known about Ca2+ mobilization in individual cells in situ. We tried to establish imaging analysis of intracellular free Ca2+ concentration ([Ca2+]i) in individual cells loaded with the acetoxymethyl ester of fluo 3 in situ, using laser scanning confocal microscopy. The method permitted us to distinguish signals from endothelial and smooth muscle cells of guinea pig artery. Addition of ATP to the artery caused a transient increase in endothelial [Ca2+]i. It was concluded that the response was induced via P2Y purinoceptors, because adenosine 5'-O-(2-thiodiphosphate), but not UTP, caused a similar response independent of extracellular Ca2+. The percentage of cells that responded to ATP (1-10 microM) and the peak amplitude of the transient increase in [Ca2+]i were dose dependently increased. Using rapid xy-scanning and line-scanning modes, we confirmed that 10 microM ATP induced Ca2+ waves, at a rate of 10-30 microns/s, after a lag time of approximately 3 s. These results show that [Ca2+]i waves within endothelial cells are physiologically induced by ATP via P2Y purinoceptor, but not P2U purinoceptor, in aortic strips in situ. The method should be of use in the study of vascular physiology and pathophysiology.

Plasma somatostatin correlates with blunted thyrotropin secretion after stimulation by thyrotropin-releasing hormone in critical illness.

To clarify whether plasma somatostatin affects thyrotropin secretion in critical illness, plasma somatostatin and thyrotropin responses to thyrotropin-releasing hormone were studied in forty-three critically ill patients. High somatostatin levels were associated with blunted thyrotropin secretion in critically ill patients. There was an inverse correlation between plasma somatostatin levels and the maximum increment of thyrotropin after stimulation by thyrotropin-releasing hormone. Decreased somatostatin and increased thyrotropin secretion before discharge from the intensive care unit were demonstrated in survivors. On the other hand, non-survivors maintained high somatostatin levels and had blunted thyrotropin secretion during their intensive care admission. These results suggest that high plasma somatostatin levels may play a role in the blunted thyrotropin secretion observed in critical illness.

[Anesthesia combined with profound hypothermia using cardiopulmonary bypass for clipping of giant basilar artery aneurysm].

A 52 year-old female was scheduled for clipping of giant basilar artery aneurysm. This operation needed temporary clipping of the basilar artery for 30-40 minutes, and preoperative examination suggested that some regions would become ischemic by temporary clipping. Therefore profound hypothermia using cardiopulmonary bypass (CPB) and thiamylal loading were planned to prevent cerebral damage during the operation. Anesthesia was induced with thiamylal, fentanyl, and isoflurane in nitrous oxide and oxygen. Following administration of vecuronium, trachea was intubated. Two hours after the start of surgery, thiamylal was titrated to obtain EEG patterns of burst-suppression before CPB and the infusion was continued until CPB was discontinued. With burst-suppression present, CPB was instituted. Hypothermia below 20 degrees C at pulmonary artery temperature was maintained until the aneurysm was clipped and bleeding from the operating site was controlled. Cooling and rewarming by CPB were carried out with ease and uneventfully. The patient had no neurological complications postoperatively.

[A case of emergency admission for CO2 narcosis in a patient with amyotrophic lateral sclerosis].

A 68-year-old man with severe dyspnea was admitted as an emergency case. He had no past history of any respiratory or neuromuscular diseases. Immediately after insufflation of oxygen, respiratory arrest occurred. The blood gas analysis showed hypoxemia and severe hypercapnia (PaO2; 32 mmHg, PaCO2; 127 mmHg). We diagnosed as CO2 narcosis, and he was treated with a respirator in the ICU. He showed nonflaccid bilateral diaphragmatic paralysis and muscle atrophy of the upper extremities. As the EMG showed giant spikes of neurogenic pattern, he was diagnosed as ALS. Weaning from the respirator failed because of his respiratory muscle fatigue. He was given rehabilitation during the day time and ventilatory support with the respirator during the night. We conclude that if we meet with an emergency patient with CO2 narcosis without any pulmonary disorder, we have to suspect neuromuscular diseases, e.q. ALS. In some of such cases, mechanical ventilation supports social rehabilitation.

Rupture of pulmonary artery induced by balloon occlusion pulmonary angiography.

A case of pulmonary artery rupture induced by balloon occlusion pulmonary angiography (BOPA) is reported. A flow-directed pulmonary artery catheter had been inserted for hemodynamic monitoring in a septic shock patient complicated by acute respiratory distress syndrome. To check for pulmonary damage, BOPA was performed immediately after hemodynamic measurement. Just as the hand injection of contrast medium was ending, the patient began to cough and a small amount of hemoptysis was observed. The angiogram showed the extravasation of contrast medium from the distal pulmonary artery to the situation of catheter tip. Pulmonary hemorrhage was controlled with mechanical ventilatory support with 10 cmH2O positive end-expiratory pressure and no specific therapy was required. This complication should be kept in mind and using a power injector to avoid injurious transient high pressure pulse is recommended.

Spinal cord ischemia after cardiac arrest.

Subsequent to cardiac arrest, a 58-year-old man with intractable dysrhythmia and severe arteriosclerosis developed flaccid paraplegia, depressed deep tendon reflexes, and showed no pain or temperature sensation caudal to Th-7 in spite of completely intact proprioception and vibration sensation. An echocardiogram showed no clots or vegetation on the prosthetic valve and no thrombus in the left atrium or left ventricle. The patient's paraplegia was permanent, at least through a follow-up period of 2 years. These findings suggest that the etiology was spinal cord ischemia due to blood supply in the area of the anterior spinal artery (ASA); however, magnetic resonance T2-weighted imaging demonstrated signal abnormalities throughout the gray matter and in the adjacent center white matter. Somatosensory-evoked potentials (SEP) measure neural transmission in the afferent spinal cord pathway, which is located in the lateral and posterior columns of the white matter; these showed a delay in latency between Th-6 and Th-7. The spinal cord is as vulnerable to transient ischemia as the brain. Spinal cord ischemia after cardiac arrest results from principal damage in the anterior horn of the gray matter, the so-called ASA syndrome; however, the pathways of SEP and pathogenesis of the spinal cord ischemia need further investigation.

Suppression of the thyrotropin response to thyrotropin-releasing hormone and its association with severity of critical illness.

OBJECTIVE: To study whether the suppression of the thyrotropin (thyroid-stimulating hormone, TSH) response to thyrotropin-releasing hormone (TRH) correlates with severity of illness and death in patients with nonthyroidal critical illness. DESIGN: Prospective study. SETTING: Intensive care unit (ICU) of a university hospital. PATIENTS: Forty-one critically ill patients without thyroid disease with multiple organ failure who were admitted to the ICU. MEASUREMENTS AND MAIN RESULTS: The TSH response to TRH was tested within 24 hrs of ICU admission. Blood samples were obtained just before, and at 15, 30, 60, 90, and 120 mins after 500-micrograms injection of synthetic TRH. Triiodothyronine, free-triiodothyronine, thyroxine, free-thyroxine and TSH concentrations were measured in the samples obtained just before TRH injection. Acute Physiology and Chronic Health Evaluation (APACHE II) scores and Sepsis scores were calculated based on the data obtained within 24 hrs of ICU admission. Individual variables were compared between survivors and nonsurvivors. The APACHE II scores and Sepsis scores of nonsurvivors were significantly higher than those scores of survivors. The overall occurrence of suppressed TSH response to TRH was 88%. Peak TSH concentration of the TSH response was significantly lower in nonsurvivors than in survivors. Serial measurement of the TSH response showed that nonsurvivors experienced a decrease in peak TSH concentration from 1.55 +/- 0.78 to 0.55 +/- 0.30 microIU/mL; in survivors, it increased from 2.10 +/- 0.26 to 7.38 +/- 1.83 microIU/mL. Conversely, the basal TSH concentration did not change in either survivors or nonsurvivors. The "severity" of illness of nonsurvivors remained high; their mean APACHE II score varied from 20.0 +/- 1.9 to 22.1 +/- 1.3 and the mean Sepsis score varied from 20.0 +/- 4.3 to 25.4 +/- 4.0, while the same scores for survivors decreased significantly (p < .05): their APACHE II score decreased from 16.2 +/- 0.7 to 7.6 +/- 2.0 and the Sepsis score went from 14.0 +/- 1.9 to 6.0 +/- 1.6. CONCLUSIONS: In critically ill patients with multiple organ failure, suppression of the TSH response to TRH frequently occurs and correlates with severity of illness and outcome. Our data indicate that measurement of the TSH response is helpful in evaluating the severity of illness and prognosis for critically ill patients.

[Hypoxic brain damage after prolonged cardiac arrest during anesthesia--changes in CT and serum NSE concentration].

A 48-year-old woman was scheduled for total hysterectomy under spinal anesthesia in a local hospital. Large doses of diazepam (20 mg) and pentazocine (30 mg) were administered for sedation five minutes after starting the operation. Four minutes later, cardiac arrest occurred. The patient did not respond to closed chest massage and was transferred to our institution. As closed chest massage was not effective because the patient was moderately obese and her abdomen was open, open chest massage was initiated with administration of a large dose of epinephrine. Five minutes later, cardiac rhythm was restored, but it had taken a total of 75 minutes to restore cardiac rhythm and the patient suffered brain death. The cause of cardiac arrest was suspected to be a lethal dose of sedatives under spinal anesthesia. CT revealed massive cerebral edema soon after resuscitation. Serum NSE (neuron specific enolase) was within normal limits (< 10 ng.ml-1) at that time, but on the following day the CT demonstrated low attenuation area of white matter and gray matter in the cerebrum and brainstem, and serum NSE increased to 357 ng.ml-1, indicating massive necrosis of neuronal cells. The high concentration of serum NSE persisted for four days, and subsequently decreased to 112 ng.ml-1. This may have been a sign of completion of washout after brain death with no cerebral perfusion. It was concluded that if a case of cardiac arrest does not respond to closed chest massage, immediate open chest massage should be considered and that serum NSE may be an indicator of prognosis of hypoxic cerebral injury.

Changes in work of breathing during continuous positive airway pressure with increased airway resistance.

STUDY OBJECTIVES: To describe the importance of measuring work of breathing (WOB) in patients with high airway resistance (Raw) during continuous positive airway pressure (CPAP) support. DESIGN: Fundamental study using an advanced model lung and a pulmonary function monitor. SETTING: A research laboratory at the ICU of a university hospital. INTERVENTIONS: Spontaneous breathing (tidal volume x respiratory rate: 400 ml x 15 min-1) was simulated with a time-cycled jet-flow generator. The CPAP and Raw were adjusted to 0, 5, and 10 cm H2O and to 5, 10, and 20 cm H2O.L-1.s-1, respectively. MEASUREMENTS AND RESULTS: Using four advanced demand-flow system type ventilators (Evita, 7200a, Servo 900C, and Servo 300), a two-bellows-in-a-box type model lung, and a pulmonary function monitor with an esophageal catheter (CP-100), we measured WOB during CPAP with increased Raw. The WOB of the model lung increased significantly with increase in CPAP. The WOB of the model lung also increased significantly with increase in Raw for all ventilators tested in this study; some values showed over 1 J.L-1. The WOB under the Servo 300 exhibited the lowest values in all situations of all the ventilators tested in this study. CONCLUSIONS: Patients with high Raw may suffer excessive WOB even during CPAP with advanced demand-flow system type ventilators. It is vital to monitor WOB continuously using an adequate pulmonary function monitor such as that used in this study.

[Phase II study of edobacomab (E5) in the treatment of gram-negative sepsis].

The efficacy, safety and usefulness of murine anti-endotoxin monoclonal IgM antibody "E5, an intravenous dose of 2 mg/kg" were evaluated in 88 patients with suspected Gram-negative sepsis from 37 institutes in Japan. Out of these, 74 patients were evaluable for the efficacy, 85 for safety and 75 for clinical usefulness. In assessing the efficacy, the patients were divided into 3 groups based on the plasma endotoxin levels (Endospecy with new PCA treatment of plasma): H group with a level of above 9.8 pg/ml and M group with a level of 3.0-9.8 pg/ml and L group with a level of below 3.0 pg/ml. 1. The efficacy rates as assessed following administration of E5 were 73.1% in the H group, 70.4% in the M group and 38.1% in the L group being higher in the groups with significantly high plasma endotoxin levels. 2. In both the H and M groups in whom plasma endotoxin levels were significantly high, the majority of the patients showed rapid reduction of the levels after administration of E5. 3. In all groups, improvement in body temperature, pulse rate, blood TNF-alpha and blood IL-6 was observed after treatment with E5. In the H and M groups with an endotoxin level of > or = 3.0 pg/ml, improvement in platelet count as well as in CRP was noted. The H group showed also improvement in WBC. 4. Improvement in the shock score was noted in all the groups but was more outstanding in the H and M groups in the early stage of treatment. 5. Side effects were seen in 5 (5.9%) of 85 patients and all thought to be allergic in symptoms such as rash, itching, fever and flare. 6. The reaction to the prick test performed before administration of E5 was negative in all these 5 patients. For 3 of the 5 patients, anti-E5 IgE antibody was measured. In all of them, the IgE levels were higher than those of healthy controls. Also, in 47.6% of patients, an elevation of anti-E5 IgG antibody was noted two weeks after the administration. 7. Clinical laboratory abnormalities were observed in 3 (3.5%) of 85 patients. They were an elevation of S-GOT.S-GPT and lowering of BUN, increased Al-p and decreased CH50, increased neutrophilia (%) and were all slight in the degree of the changes. 8. The clinical usefulness of E5 was evaluated for 75 patients.(ABSTRACT TRUNCATED AT 400 WORDS)

[Rupture of asymptomatic mycotic aneurysm after valve replacement in infective endocarditis].

Mycotic cerebral aneurysms (MCA) are one of the most serious complications of infective endocarditis. The rupture of MCA in patients under anticoagulant therapy following valve replacement carries high mortality. We encountered this serious complication in a patient who had no neurologic symptoms. A 12-year-old girl was scheduled for mitral valve replacement (MVR) 5 weeks after antibiotic therapy for infective endocarditis caused by Staphylococcus aureus. Before the surgery, she did not have any neurologic symptoms or abnormal findings in CT scanning examination. The surgery to remove her mitral valve with bacterial vegetations and replace it with an artificial valve proceeded smoothly and she appeared to begin an uneventful postoperative recovery. However, she suddenly began to complain of severe headache and became unconscious on the fifth days after MVR. A CT scan showed cerebral herniation due to a major subdural hematoma. A ruptured MCA was detected in the orbito-frontal artery and clipped in an emergency operation. She was transferred to the intensive care unit and given continuous infusion of barbiturate to prevent increase of her intracranial pressure. CT scanning and arteriography 10 days after the MCA clipping, revealed a new subdural hematoma and MCA just proximal to the previous clip. It is important to bear in mind that patients with infective endocarditis can have mycotic cerebral aneurysms without any clinical neurologic symptoms.

Prolongation of tetracaine spinal anesthesia by oral clonidine.

The effects of oral clonidine on the duration of isobaric tetracaine spinal anesthesia were studied in 30 patients undergoing urologic procedures. All patients received 15 mg of tetracaine intrathecally in isobaric saline solution. Group 1 (n = 10) received 0.25 mg of oral triazolam; group 2 (n = 10) received 0.15 mg of oral clonidine; and group 3 (n = 10) received 0.25 mg of oral triazolam and 0.75 mg of intrathecal phenylephrine. In group 1, the times for two- and four-segment regression of the level of analgesia to pin-prick were 80 +/- 17 and 123 +/- 22 min, respectively (mean +/- SD). The corresponding values of those measurements were 170 +/- 27 and 273 +/- 48 min in group 2 and 175 +/- 34 and 273 +/- 68 min in group 3. All the regression times in groups 2 and 3 were significantly longer than those in group 1. Regression times were not different between groups 2 and 3. The authors conclude that prolongation of tetracaine sensory analgesia may be produced by premedication with 0.15 mg of oral clonidine. The prolongation is similar to that produced by intrathecal phenylephrine.

[Continuous infusion of ketamine and midazolam for prolonged sedation in the intensive care unit].

The clinical effects and pharmacokinetics of ketamine and midazolam, administered continuously for prolonged sedation were studied in 7 critically ill patients under mechanical ventilation. Initially ketamine 1 mg.kg-1 and midazolam 0.1 mg.kg-1 were administered intravenously and these were followed by infusion at a rate of 1.0 mg.kg-1.hr-1 of ketamine and 0.05 mg.kg-1.hr-1 of midazolam. The infusion rate was changed every 30 minute with increments of 0.5 mg.kg-1.hr-1 of ketamine and 0.05 mg.kg-1.hr-1 of midazolam until the sedative score by Ramsy RAE reached rank 4 (i.e. slow response to loud verbal commands). The plasma concentrations of ketamine were analyzed using high performance liquid chromatography and those of midazolam using gas chromatography. The mean maintenance doses of ketamine and midazolam were 2.25 +/- 0.61 mg.kg-1.hr-1 and 0.11 +/- 0.05 mg.kg-1.hr-1 (mean +/- SD), respectively. There were no significant changes in blood pressure or heart rate before and after the injection of ketamine and midazolam in all the patients. The plasma concentrations of ketamine and midazolam were 2.98 +/- 0.20 micrograms.ml-1 and 494.1 +/- 66.7 ng.ml-1, respectively. The time to clear response to verbal commands after cessation of the continuous infusion was 168 +/- 109 min. The plasma concentrations of ketamine and midazolam decreased rapidly, and plasma half-life of ketamine was about 1 hour and for midazolam less than 2 hours. In conclusion, continuous infusion of ketamine and midazolam was very useful to sedate critically ill patients under mechanical ventilation, with minimal effect on the cardiovascular system and rapid recovery of consciousness.