Hiromasa Nagata

Sepsis-induced cardiac dysfunction and β-adrenergic blockade therapy for sepsis

Despite recent advances in medical care, mortality due to sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, remains high. Fluid resuscitation and vasopressors are the first-line treatment for sepsis in order to optimize hemodynamic instability caused by vasodilation and increased vascular permeability. However, these therapies, aimed at maintaining blood pressure and blood flow to vital organs, could have deleterious cardiac effects, as cardiomyocyte damage occurs in the early stages of sepsis. Recent experimental and clinical studies have demonstrated that a number of factors contribute to sepsis-induced cardiac dysfunction and the degree of cardiac dysfunction is one of the major prognostic factors of sepsis. Therefore, strategies to prevent further cardiomyocyte damage could be of crucial importance in improving the outcome of sepsis.Among many factors causing sepsis-induced cardiac dysfunction, sympathetic nerve overstimulation, due to endogenous elevated catecholamine levels and exogenous catecholamine administration, is thought to play a major role. β-adrenergic blockade therapy is widely used for ischemic heart disease and chronic heart failure and in the prevention of cardiovascular events in high-risk perioperative patients undergoing major surgery. It has also been shown to restore cardiac function in experimental septic animal models. In a single-center randomized controlled trial, esmolol infusion in patients with septic shock with persistent tachycardia reduced the 28-day mortality. Furthermore, it is likely that β-adrenergic blockade therapy may result in further beneficial effects in patients with sepsis, such as the reduction of inflammatory cytokine production, suppression of hypermetabolic status, maintenance of glucose homeostasis, and improvement of coagulation disorders.Recent accumulating evidence suggests that β-adrenergic blockade could be an attractive therapy to improve the prognosis of sepsis. We await a large multicenter randomized clinical trial to confirm the beneficial effects of β-adrenergic blockade therapy in sepsis, of which mortality is still high.

Transient hemodynamic change and accuracy of arterial blood pressure-based cardiac output.

BACKGROUND: The purpose of this study was to determine the effects of transient arterial blood pressure change on the accuracy of the FloTrac™/Vigileo™ monitor (Edwards Lifesciences, Irvine, CA). METHODS: We compared stroke volume determined with the FloTrac/Vigileo with Doppler during anesthetic induction in 20 patients undergoing abdominal aortic reconstruction. RESULTS: The difference between the FloTrac measurements of stroke volume and the Doppler measurements of stroke volume was −7.5 ± 20.5 mL (mean ± SD) before induction, 0.3 ± 14.9 before laryngoscopy, 17.5 ± 26.9 during laryngoscopy, 20.5 ± 27.6, and −4.5 ± 16.4 mL 3 minutes after endotracheal tube placement. CONCLUSION: The FloTrac/Vigileo measured stroke volume with reasonable accuracy during transient hypotension but overestimated stroke volume during transient hypertension.

Response Time of Different Methods of Cardiac Output Monitoring During Cardiopulmonary Resuscitation and Recovery

partial pressure (PETCO2) and mixed venous hemoglobin oxygen saturation (SvO2) also were continuously monitored and recorded. During the laparotomy, hypotension and tachycardia were noted and were accompanied by facial flushing. This was diagnosed as mesenteric traction syndrome and was treated with fluid administration and intermittent intravenous ephedrine. During this period, high cardiac output was recorded with all devices. The maximal values recorded were 6.9 L/min, 9.2 L/min, 17.4 L/min, and 17.9 L/min via the EDM, NICO, STAT CCO, and trend CCO monitors, respectively. At this point, the SvO2 was 89% and VCO2 was 137 mL/min. These symptoms eventually disappeared, and the patient’s CO subsequently stabilized (measured as 5.5 L/min, 5.1 L/min, 10.1 L/min, and 11.3 L/min via the EDM, NICO, STAT CCO, and CCO monitors, respectively; SvO2 85%, VCO2 126 mL/min. The CO at this point as measured with a bolus thermodilution was 7.0 L/min. During surgical exposure of the aortic aneurysm, a sudden onset of ventricular premature contraction was followed by sustained ventricular tachycardia (VT). Because initial DC cardioversion failed to stop the VT, phenylephrine, lidocaine, nitroglycerin, and epinephrine were administered while closed-chest compression was provided. During CPR, the patient was manually ventilated to ensure adequate ventilation. The minute volume provided during CPR was between 11 L/min and 12 L/min. The third DC cardioversion finally restored the patient to sinus rhythm. The duration of VT was 9 minutes, and chest compression provided a systolic pressure of more than 60 mmHg and diastolic pressure of more than 20 mmHg during CPR. The trend for the EDM, NICO, STAT CCO, and trend CCO monitors are summarized in Figure 1, along with PETCO2 and SvO2 during the CPR period. The CO measured with EDM varied from 0 to 2.5 L/min, and the signal of descending aortic blood flow caused by chest compression was clearly visible during this event using EDM. Three rebreathing cycles were used with a NICO monitor during CPR. The first rebreathing cycles were applied at 2 minutes after the onset of VT and the CO and VCO2 were reported as 2.9 L/min and 104 mL/min, respectively. The second cycle was applied 5 minutes after the onset of VT and failed to estimate the CO. The third rebreathing cycle was applied at 8 minutes after the onset of VT, and the CO and VCO2 were

Psychological and endocrine factors and pain after mastectomy

This prospective study was designed to examine the associations of demographic, clinical, psychological and neuroendocrine factors with acute and chronic post‐operative pain following partial mastectomy.

Evaluation of the site specificity of acute disuse muscle atrophy developed during a relatively short period in critically ill patients according to the activities of daily living level: A prospective observational study

INTRODUCTION In critically ill patients, excessive bed rest and immobilisation have been shown to cause disuse muscle atrophy, which contributes to prolonged hospitalisation and decreased activity of daily living (ADL) levels. However, the degree and site specificity of acute disuse muscle atrophy in critically ill patients during a relatively short intensive care unit (ICU) stay have not been fully elucidated. METHODS Critically ill patients, who required bed rest on ICU admission, were eligible for this study. The degree of skeletal muscle atrophy was evaluated on the day of, and 72 and 144h after ICU admission by measuring the limb circumference in ADL-dependent or -independent patients separately at five different sites: the midpoint of the upper limb between the acromion and the olecranon, the maximum diameter of the triceps surae in the lower leg, and three different sites in the thigh at 5, 10, and 15cm above the superior pole of the patella. Value of the limb circumference was presented as a percentage relative to the baseline (median). RESULTS In ADL-dependent patients, limb circumferences at all five sites were decreased significantly at 144h compared with the baseline (98.9-100% in the upper limbs, 97.1-97.2% in the lower legs, and 96.5-99.1% in the thighs), but not at 72h. In contrast, the limb circumferences at almost all sites decreased significantly at both 72 and 144h (100% in the upper limbs, 94.5-94.7% in the lower legs, and 89.7-94.7% in the thighs), compared with the baseline in ADL-independent patients. Muscle atrophy was greater at the four different lower-limb sites compared to the upper limb during 144h in the ICU in the ADL-independent, but not in the ADL-dependent patients. CONCLUSIONS Compared to ADL-dependent patients, ADL-independent patients are prone to develop muscle weakness, especially in the lower limbs.

Descending aortic blood flow during aortic cross-clamp indicates postoperative splanchnic perfusion and gastrointestinal function in patients undergoing aortic reconstruction

BACKGROUND The purpose of this observational study was to investigate the relationship between splanchnic and renal blood flow during infrarenal aortic cross-clamp (XC) and postoperative gastrointestinal perfusion and function. METHODS Descending aortic blood flow (DABF) was continuously monitored with an oesophageal Doppler monitor (Cardio-Q, Deltex Ltd, Chichester, UK) in 31 patients undergoing elective abdominal aortic aneurysm repair. Cardiac output (CO) was determined by indocyanine green dilution before, during, and after XC. Perioperative gastrointestinal perfusion was assessed by gastric intramucosal pH (pHi, Tonocap, GE Healthcare, Helsinki, Finland). Postoperative gastrointestinal recovery was assessed by the number of postoperative days until the patient successfully resumed solid food intake. The relationship between the mean DABF during XC and gastric pHi after XC release and postoperative gastrointestinal recovery was analysed with Spearmans correlation coefficient. RESULTS accounted for ∼ 55% of CO during XC and significantly decreased during XC, despite arterial pressure remaining within an optimal range. There were two distinct relationships between DABF during XC and gastric pHi after XC release. Gastric pHi steeply and linearly declined when indexed DABF was below 0.82 litre min(-1) m(-2). Above this critical value, there was no linear relationship between them. The duration of postoperative gastrointestinal dysfunction was inversely correlated with the mean DABF during XC. The best cut-off value of the mean indexed DABF during XC to prevent prolonged gastrointestinal dysfunction was 1.2 litre min(-1) m(-2). CONCLUSIONS Decreased DABF during XC associates splanchnic hypoperfusion after XC release and delayed recovery of gastrointestinal function.

Can mixed venous hemoglobin oxygen saturation be estimated using a NICO monitor

BACKGROUND: We hypothesized that mixed venous hemoglobin oxygen saturation (SvO2) can be estimated by calculation from CO2 production, cardiac output, and arterial oxygen saturation measured using a noninvasive cardiac output (NICO) monitor (Novametrix-Respironics, Wallingford, CT). METHODS: Twenty-three patients undergoing aortic aneurysm repair underwent SvO2 monitoring using a pulmonary artery catheter and cardiac output monitoring using a NICO monitor. The estimated SvO2 value calculated from NICO monitor-derived values was compared with the SvO2 value measured using a pulmonary artery catheter. The accuracy of this estimation was analyzed with Bland-Altman method. The ability of this estimation to track the change of SvO2 was also evaluated using correlation analysis to compare the changes of estimated SvO2 and measured SvO2. RESULTS: The bias ± limits of agreement of the estimated SvO2 against measured SvO2 was −2.1% ± 11.2%. The change of estimated SvO2 was modestly correlated with the change of measured SvO2. CONCLUSIONS: SvO2 derived from the values measured by the NICO monitor cannot be used interchangeably with the values measured spectrophotometrically using the pulmonary artery catheter. More refinement is required to obtain more reliable estimate of SvO2 less invasively. However, large changes of SvO2 may be detected with this method and can be used as a precautionary sign when the balance between oxygen supply and demand is compromised without inserting a central venous catheter.

Difference in autologous blood transfusion-induced inflammatory responses between acute normovolemic hemodilution and preoperative donation

PurposeThe inflammatory response triggered by transfusion is implicated in the pathophysiology of transfusion-related immunomodulation. The authors hypothesized that two distinctive autotransfusion methods, acute normovolemic hemodilution (ANH) and preoperative donation (PD), have different influences on both inflammatory mediator generation during storage and the inflammatory response after a transfusion. The purpose of this study was to compare the plasma concentrations of neutrophil elastase (NE), interleukin (IL)-6, IL-8, and IL-10 in patients who underwent either of these two autologous transfusion methods.MethodsWith institutional review board approval, the plasma concentrations of the above inflammatory mediators were determined in 23 patients with ANH and 8 patients with PD at the following time points: after anesthetic induction, at the end of the operation, and the morning of postoperative day 1. The concentrations of these inflammatory mediators were also measured in the donated blood obtained by either ANH or PD before retransfusion.ResultsThe mean storage durations were 3.7 h and 6.1 days for ANH and PD, respectively. Higher concentrations of NE and IL-10 were detected in the PD blood than in the ANH blood. Long duration of storage and/or low temperature may have been responsible for the increased NE and IL-10 concentrations in the PD blood. However, the difference between the two groups in the extent of increased plasma concentrations of these inflammatory mediators was not statistically significant.ConclusionInflammatory mediators were significantly increased in PD blood during storage compared to the blood obtained by ANH. However, their effects on the inflammatory response elicited in the recipients were not significantly different.

Increased prothrombotic property as a risk factor of acute kidney injury after surgical repair of abdominal aortic aneurysm: A prospective observational study

BackgroundAcute kidney injury (AKI) is one of the major morbidities after surgical repair of abdominal aortic aneurysm (AAA); however, precise pathogenesis of this morbidity has not been well determined. Since prothrombotic coagulation abnormality may precede organ dysfunction in systemic inflammatory state, we examined the kinetics of von Willebrand factor (VWF) and a disintegrin-like metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13), a cleaving enzyme of VWF, on the development of AKI after AAA surgery.MethodsThe kinetics of ADAMTS13 and VWF were examined in ten patients who underwent surgical repair of AAA. The changes in plasma neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker for AKI, and serum creatinine concentration were also examined at four points until seventh postoperative day (POD). Clinical diagnosis of AKI was based on the change in serum creatinine concentration and urine output according to Acute Kidney Injury Network (AKIN) criteria.ResultsADAMTS13 activity was significantly lower than normal level before the surgery and showed a trend of decrease toward 3POD. The VWF/ADAMTS13 ratio showed a significant increase on 1POD, which persisted until 7POD. None of patents was diagnosed as AKI based on AKIN criteria, although two patients received furosemide and/or carperitide therapy because of decreased urine output less than 0.5 ml/kg/h for several hours in ICU. Plasma NGAL showed a trend to increase after the surgery, which was significant on 3POD. The change in plasma NGAL was significantly correlated with VWF/ADAMTS13 ratio (P < 0.01).ConclusionsThis study has shown that patients undergoing AAA surgery were prothrombotic after the surgery because of high VWF/ADAMTS13 ratio. Correlation between VWF/ADAMTS13 ratio and NGAL might indicate contribution of thrombotic event to subclinical AKI in the patients undergoing AAA surgery.