Methidathion Poisoning.

Although methidathion is an organophosphate insecticide, it is different from the other organophosphates in terms of toxicity. Because of its relatively high fat solubility, the apparent volume of methidathion distribution throughout the body is very high, indicating that hemoperfusion is not effective in removing this organophosphate from the body. Redistribution of methidathion from fat to blood can also occur when plasma levels diminish. Additionally, acetylcholinesterase aging, which is the loss of an alkyl side chain that prevents reactivation by oximes, is very rapid so that the effective reactivation by oximes is thwarted. Thus, methidathion's effect on acetylcholinesterase inhibition is long lasting, particularly with a high dose. In addition to its parasympatholytic effect and ability to induce muscle paralysis, methidathion poisoning is associated with a profound and long-lasting circulatory collapse due to sympathetic ganglion blockade. This report presents the case of a 55-year-old man who accidentally ingested a high dose of methidathion. He later developed enteroinvasive aspergillosis infection-induced multiple bowel perforations on two separate occasions while on mechanical ventilator support, resulting in a fatal outcome. The renin-angiotensin axis activated by sympathetic ganglion blockade may have reduced the patient's splanchnic blood flow, contributing to translocation of endotoxin. Also, the effect of excessive acetylcholine on non-neuronal acetylcholine receptors may have contributed to the development of fatal enteroinvasive aspergillosis in this patient.

Veno-veno-arterial ECMO support for acute myocarditis combined with ARDS: a case report.

BACKGROUND: In patients who developed a combined situation of severe acute respiratory distress syndrome with refractory hypoxemia and acute cardiac failure with circulatory collapse, traditional veno-venous or veno-arterial extracorporeal membrane oxygenation approach alone may not be sufficient enough to maintain both an acceptable range of gas exchange and a hemodynamic stability. CASE REPORT: A 27-year-old male patient was suffering from severe acute respiratory distress syndrome caused by community-acquired pneumonia and acute myocarditis with circulatory shock. After mechanical ventilation for respiratory support, he was in a persistently refractory shock state. Veno-veno-arterial mode of extracorporeal membrane oxygenation was thus applied to provide both respiratory and circulatory support simultaneously, with good success. DISCUSSION: Modifying to a veno-veno-arterial mode can be another alternative strategy in a combined situation of refractory respiratory and cardiac failure, thus providing not only respiratory support but also circulatory support. In veno-veno-arterial mode, the returning circuit from the pump was divided with a Y connector into 2 reinfusion circuits; each reinfusion circuit was connected to the contralateral side femoral vein and artery, respectively. The distribution of reinfusion flow was adjusted depending on the patient's cardiopulmonary status. CONCLUSIONS: Although there is no consensus about the veno-veno-arterial mode of extracorporeal membrane oxygenation, this combined mode can be helpful in patients with acute refractory respiratory and cardiac failure, as shown in the present case. We need further experience and improvements in the circuit system used in the veno-veno-arterial mode of ECMO.

Nafamostat mesilate as a regional anticoagulant in patients with bleeding complications during extracorporeal membrane oxygenation.

PURPOSE: Anticoagulation is mandatory for extracorporeal membrane oxygenation (ECMO), but systemic heparinization, which has been most widely used as an anticoagulant, has been associated with bleeding complications. The present study reviewed the usefulness and safety of nafamostat mesilate as a regional anticoagulant in patients with bleeding complication during ECMO. METHODS: We retrospectively reviewed the record of 13 cases. The nafamostat mesilate dose was regulated to maintain the activated clotting time (ACT) or activated partial thromboplastin time (aPTT) values within an adequate range at the ECMO reinfusion route. ACT or aPTT values in blood samples from the ECMO circuit and from the patients were measured simultaneously and consecutively. RESULTS: We measured the ACT value in 6 cases and aPTT in 7 cases. The bleeding complications were treated in 11 cases. When we compared the difference in 2 anticoagulation values (ACT and aPTT) between the 2 blood samples, one taken from ECMO and the other from patients, mean anticoagulation values of blood from patients were lower than those from ECMO circuit in 11 cases. With respect to the type of ECMO reinfusion mode, the difference was significant only in veno-arterial mode ECMO group (p<0.001). CONCLUSIONS: Nafamostat mesilate, with which we can reduce anticoagulation values of patient to a safe level without losing the ECMO anticoagulation values is expected to be useful as a regional anticoagulant in patients with bleeding complications or a high risk of bleeding during ECMO.

PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing.

Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on Escherichia coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles.

Change in pulmonary blood volume changes pulmonary artery systolic storage.

BACKGROUND: A fraction of right ventricular stroke volume (pulmonary artery systolic storage, [PASS]), which is stored in pulmonary arteries during systole and then discharged to the capillaries, determines the diastolic pulmonary capillary blood flow and hence the capillary blood volume participating in gas diffusion. Possibility that increases in pulmonary blood volume (PBV) increase PASS, leading to an improved distribution of ventilation-to-perfusion ratios (V/Q), was examined. METHODS AND RESULTS: Included were 34 obese patients undergoing bariatric surgery. We used a nitrous oxide-airway-pneumotachographic method to measure PASS. The measurements were repeated before and after increasing PBV. In 20 patients, PBV was increased with infusion of crystalloids, which was guided by pulmonary capillary wedge pressure (PCWP). There was a good correlation between change in PASS and change in PBV (r(2) = 0.741, P < 0.0001). However, when the baseline PASS was high, changes in PASS were much less. In patients with a pulmonary artery diastolic-pulmonary capillary wedge pressure gradient ≥ 6 mmHg, the baseline PASS was correlated with pulmonary venous resistance (r(2) = 0.644, P = 0.017). In 14 patients, in whom PBV was increased with both changes in position and infusion of crystalloids, the physiologic dead space-to-tidal volume ratio (VD/VT) was measured as an index of the distribution of V/Q. There was a good negative correlation between PASS and VD/VT (r(2) = 0.697, P < 0.0001). However, at a high baseline PASS, increases in PBV decreased PASS (P = 0.0006) and increased VD/VT (P = 0.0018). CONCLUSIONS: Changes in PBV change PASS and thereby the distribution of V/Q, depending on pulmonary venous resistance, which determines the baseline PASS.

Increased pulmonary artery systolic storage associated with improved ventilation-to-perfusion ratios in acute respiratory distress syndrome.

PURPOSE: The possibility that the increased pulmonary artery systolic storage (PASS) correlates with an improved distribution of ventilation/perfusion (V(A)/Q) and hence benefits gas exchange in acute respiratory distress syndrome (ARDS) was examined. Pulmonary artery systolic storage is the fraction of stroke volume stored in PA during systole and then discharged to the capillaries. The increased PASS can augment the diastolic pulmonary capillary blood flow (PCBF), which can then increase capillary blood volume participating in gas diffusion. We examined this by assessing the correlation between PASS and physiologic dead space to tidal volume (VD/VT) ratio. MATERIALS AND METHODS: Included were 17 patients with ARDS. By using nitrous oxide-airway-pneumotachographic method, we measured the instantaneous PCBF, from which PASS was determined. Because PASS is the same as the flow volume of PCBF during diastole, PASS was determined from the flow volume of PCBF during diastole divided by the flow volume of PCBF during a whole cardiac cycle. The VD/VT ratio, used as an index of V(A)/Q, was measured by using the Bohr equation. RESULTS: There was a good inverse correlation between PASS and VD/VT (r(2) = 0.785, P < .0001). CONCLUSIONS: Our data indicate that the increased PASS correlates with an improved distribution of V(A)/Q and hence benefits gas exchange in ARDS.

Increased pulmonary venous resistance in morbidly obese patients without daytime hypoxia: clinical utility of the pulmonary artery catheter.

BACKGROUND: The pulmonary artery (PA) diastolic-pulmonary capillary wedge pressure (PAD-PCWP) gradient has been shown to be increased in morbidly obese patients without daytime hypoxia. In sepsis, the increased pulmonary venous resistance (PvR) contributes to increases in PAD-PCWP gradient. In addition, the obesity-related endotoxemia is known to be involved in the pathophysiology of metabolic syndrome in obesity. Therefore, it is possible that the increased PvR contributes to increases in PAD-PCWP gradient in morbid obesity. We examined this possibility. METHODS: Included were 25 obese patients without daytime hypoxia undergoing bariatric surgery under general anesthesia. PvR was calculated as the difference between mean PA output pressure and PCWP divided by cardiac index. Mean PA output pressure was computed from the harmonic form of the recorded PA pressure by applying an attenuating factor to its phasic components, for which Fourier analysis was used. Total pulmonary vascular resistance (TPVR) was calculated as the difference between mean PA pressure and PCWP divided by cardiac index. To avoid the effect of PA resistance on TPVR and PvR, the PvR/TPVR ratio was used. RESULTS: There was a good correlation between PvR/TPVR ratio and PAD-PCWP gradient (r2=0.785, P<0.0001). When patients were divided into two groups based on PAD-PCWP gradient, the PvR/TPVR ratio was 0.67+/-0.06 (mean+/-SD) in the group with a PAD-PCWP gradient of at least 6 mmHg and 0.48+/-0.05 in the other group (P<0.0001). CONCLUSIONS: A strong correlation between PvR/TPVR ratio and PAD-PCWP gradient suggests that the increased PvR contributes to increased PAD-PCWP gradient in obese patients without daytime hypoxia.

Estimated right ventricular systolic time intervals for the assessment of right ventricular function in acute respiratory distress syndrome.

Right ventricular (RV) systolic time intervals (STIs) have been shown to accurately reflect RV function in patients with acute respiratory distress syndrome (ARDS). The measurement of RVSTIs requires phonocardiography to define the time of RV end systole. If RV end-systolic pressure (RVESP) can be derived from peak pulmonary artery (PA) systolic pressure, then the time of RV end systole, and hence, RVSTIs can be deduced without phonocardiography. We tested this possibility. In 34 patients with ARDS, RVESP was determined on the PAP curve at RV end systole, which was defined by phonocardiography. The ratios of RVESP/peak PA systolic pressure were obtained in each patient, the mean of which was 0.90 +/- 0.006. With an application of this value, the estimated RVSTIs were determined in other groups of patients. Right ventricular end-systolic pressure was estimated from the peak PA systolic pressure by multiplying 0.9. Then the point of RV end systole was determined on the electrocardiographic tracing that coincided with the point of RVESP on the PAP curve by simultaneous display of electrocardiograph and PAP curve. Total electromechanical systole was measured from the onset of the QRS complex to the point of RV end systole on the electrocardiograph. The onset of RV ejection was defined by PAP curve. The validity of this estimated RVSTIs was tested by comparing with the measured RVSTIs. By Bland-Altman analysis, the mean difference in RVSTIs between the two methods was 0.007, and bias was 0.0036, suggesting close agreement. The estimated RVSTIs can be used to accurately assess RV function.

Right ventricular systolic function is not depressed in morbid obesity.

BACKGROUND: The increased pulmonary blood volume associated with the increased total blood volume in morbidly obese patients increases pulmonary artery pressure and pulmonary vascular resistance, resulting in increased right ventricular (RV) afterload. Thus, the morbidly obese may develop RV dysfunction owing to the increased RV afterload. We examined this possibility by assessing RV contractile function in morbidly obese patients, using RV end-systolic pressure-volume relationship and RV systolic time intervals. METHODS: Included were 25 morbidly obese patients undergoing gastric bypass surgery under general anesthesia. Pulmonary artery pressure and RV end-systolic volume were measured with a thermodilution pulmonary artery catheter. Pulmonary arterial dicrotic notch pressure was used as an estimate of RV end-systolic pressure. Two data points were used to define RV end-systolic pressure-volume relationship. RV systolic time intervals were determined by simultaneous graphic display of the electrocardiograph, phonocardiograph, and pulmonary artery pressure curve, and were expressed as a pre-ejection period/RV ejection time ratio. RESULTS: The mean slope of right ventricular end-systolic pressure-volume relationship line was 0.54 +/- 0.13 and mean pulmonary vascular resistance 274 +/- 80 dyne.sec.cm(-5).m(-2). The mean pre-ejection period/RV ejection time ratio was 0.4 +/- 0.11. There was an inverse correlation between the pre-ejection/RV ejection time ratio and the slope of RV end-systolic pressure-volume relationship line (R(2)=0.658, P<0.0001). CONCLUSION: Our data indicate that RV function is not depressed in morbid obesity despite increased RV afterload.

Increased pulmonary venous resistance contributes to increased pulmonary artery diastolic-pulmonary wedge pressure gradient in acute respiratory distress syndrome.

BACKGROUND: Pulmonary artery diastolic (PAD)-pulmonary wedge pressure (PWP) gradient has been shown to be increased in sepsis and acute respiratory distress syndrome (ARDS). Because pulmonary venous vasoconstriction induced by endotoxemia in sepsis or postcapillary leukocyte aggregation in ARDS or both can increase pulmonary venous resistance (Rpv), it is possible that the elevated Rpv increases PAD-PWP. The authors examined this possibility by assessing the correlation between Rpv and PAD-PWP gradient in patients with ARDS. METHODS: Included were 20 patients with ARDS who required surgical procedures during general anesthesia. Rpv was calculated as the difference between mean pulmonary artery (PA) output pressure and PWP divided by cardiac index. Mean PA output pressure was computed from harmonic form of the recorded PA pressure by applying an attenuating factor to its phasic components, for which Fourier analysis was used. Total pulmonary vascular resistance (TPVR) was calculated as the difference between mean PA input pressure and PWP divided by cardiac index. To avoid the effect of PA resistance on TPVR and Rpv, the relative pulmonary venous resistance (Rpv/TPVR) was used. RESULTS: There was a good correlation between Rpv/TPVR and PAD-PWP gradient (R = 0.698, P < 0.0001). When patients were classified into two groups based on PAD-PWP gradient, the Rpv/TPVR was 0.66 +/- 0.06 in the group with a PAD-PWP gradient of 6 mmHg or greater and 0.46 +/- 0.08 in the other group (P < 0.0001). CONCLUSION: A strong correlation between Rpv/TPVR and PAD-PWP gradient suggests that the increased Rpv contributes to increased PAD-PWP gradient in patients with ARDS.

Acute respiratory distress syndrome of the contralateral lung after reexpansion pulmonary edema of a collapsed lung.

STUDY OBJECTIVE: To report that leukocyte-mediated acute injury may develop in a nonhypoxic lung after hypoxia-reoxygenation injury of the hypoxic lung and in other systemic organs in patients with reexpansion pulmonary edema. DESIGN: Case report analysis with examination of the literature. SETTING: Intensive care unit of a university hospital. PATIENTS: Three patients who developed leukocyte-mediated acute lung injury in the contralateral lung and systemic organ injury after ipsilateral reexpansion pulmonary edema of a collapsed lung. MEASUREMENTS: To rule out the possibility that the acute lung injury in the contralateral lung was an extension of the hypoxia-reoxygenation injury, we analyzed changes in leukocyte and platelet count in the peripheral blood in relation to the development of pulmonary edema in each lung. Changes in liver enzymes were also analyzed to detect hepatic dysfunction as evidence of systemic organ injury. MAIN RESULTS: Both leukocyte and platelet counts decreased when reexpansion pulmonary edema developed, and decreased further when acute lung injury developed in the contralateral lung (F = 8.42, p = 0.037 for leukocytes, and F = 17.66, p = 0.01 for platelets). Significant hepatic dysfunction developed, as evidenced by increases in both serum bilirubin (p = 0.001) and lactic dehydrogenase, indicating the presence of systemic organ injury. CONCLUSIONS: The hypoxia-reoxygenation injury of one lung can induce acute lung injury in the other lung and systemic organ injury.