Central Venous Levels Research Articles

Transpulmonary Plasma Endothelin-1 Arterial:Venous Ratio Differentiates Survivors from Non-Survivors in Critically Ill Patients with COVID-19-Induced Acute Respiratory Distress Syndrome.

Endothelin-1 (ET-1) is a potent vasoconstrictor produced by endothelial cells and cleared from circulating blood mainly in the pulmonary vasculature. In a healthy pulmonary circulation, the rate of local production of ET-1 is less than its rate of clearance. In the present study, we aimed to investigate whether the abnormal pulmonary circulatory handling of ET-1 relates to poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS). To this end, central venous and systemic arterial ET-1 plasma levels were simultaneously measured on Days 1 and 3 following ICU admission in mechanically ventilated COVID-19 patients with ARDS (COVID-19 ARDS, N = 18). Central venous and systemic arterial ET-1 plasma levels were also measured in two distinct SARS-CoV-2-negative mechanically ventilated critically ill patient groups, matched for age, sex, and critical illness severity, with ARDS (non-COVID-19 ARDS, N = 14) or without ARDS (non-COVID-19 non-ARDS, N = 20). Upon ICU admission, COVID-19-induced ARDS patients had higher systemic arterial and central venous ET-1 levels compared to the non-COVID-19 ARDS and non-COVID-19 non-ARDS patients (p < 0.05), yet a normal systemic arterial:central venous (A:V) ET-1 ratio [0.63 (0.49-1.02)], suggesting that pulmonary ET-1 clearance is intact in these patients. On the other hand, the non-COVID-19 ARDS patients demonstrated abnormal ET-1 handling [A:V ET-1 ratio 1.06 (0.93-1.20)], while the non-COVID-19 non-ARDS group showed normal ET-1 handling [0.79 (0.52-1.11)]. On Day 3, the A:V ratio in all three groups was <1. When the COVID-19 ARDS patients were divided based on 28-day ICU mortality, while their systemic arterial and central venous levels did not differ, the A:V ET-1 ratio was statistically significantly higher upon ICU admission in the non-survivors [0.95 (0.78-1.34)] compared to the survivors [0.57 (0.48-0.92), p = 0.027]. Our results highlight the potential importance of ET-1 as both a biomarker and a therapeutic target in critically ill COVID-19 patients. The elevated A:V ET-1 ratio in non-survivors suggests that the early disruption of pulmonary ET-1 handling may be a key marker of poor prognosis.

Does patient position during liver surgery influence the risk of venous air embolism?

Background: It is generally believed that positioning of the patient in a head-down tilt (Trendelenberg position) decreases the likelihood of a venous air embolism during liver resection. Methods: The physiological effect of variation in horizontal attitude on central and hepatic venous pressure was measured in 10 patients during liver surgery. Hemodynamic indices were recorded with the operating table in the horizontal, 20 degrees head-up and 20 degrees head-down positions. Results: There was no demonstrable pressure gradient between the hepatic and central venous levels in any of the positions. The absolute pressures did, however, vary in a predictable way, being highest in the head-down and lowest during head-up tilt. However, on no occasion was a negative intraluminal pressure recorded. Conclusion: The effect on venous pressures caused by the change in patient positioning alone during liver surgery does not affect the risk of venous air embolism.

The nitric oxide synthase cofactor tetrahydrobiopterin reduces allograft ischemia-reperfusion injury after lung transplantation

Objective: Exogenous nitric oxide reduces ischemia-reperfusion injury after solid organ transplantation. Tetrahydrobiopterin, an essential cofactor for nitric oxide synthases, may restore impaired endothelium-dependent nitric oxide synthesis. We evaluated whether tetrahydrobiopterin administration to the recipient attenuates lung reperfusion injury after transplantation in swine. Methods: Unilateral left lung transplantation was performed in 15 weight-matched pigs (24-31 kg). Donor lungs were flushed with 1.5 L cold (1°C) low-potassium-dextran solution and preserved for 20 hours. Group I animals served as controls. Group II and III animals were treated with a bolus of tetrahydrobiopterin (20 mg/kg). In addition, in group III a continuous infusion of tetrahydrobiopterin (10 mg/kg per hour over 5 hours) was given. One hour after reperfusion, the recipient right lung was occluded. Cyclic guanosine monophosphate levels were measured in the pulmonary venous and central venous blood. Extravascular lung water index, hemodynamic variables, lipid peroxidation, and neutrophil migration to the allograft were assessed. Results: In group III a significant reduction of extravascular lung water was noted in comparison with the controls ( P = .0047). Lipid peroxidation in lung allograft tissue was significantly reduced in group II ( P = .0021) and group III ( P = .0077) in comparison with group I. Pulmonary venous levels of cyclic guanosine monophosphate increased up to 23 ± 1 pmol/mL at 5 hours in group II and up to 40 ± 1 pmol/mL in group III (group I, 4.1 ± 0.5 pmol/mL [I vs III]; P < .001), whereas central venous levels of cyclic guanosine monophosphate were unchanged in all groups. Conclusion: Tetrahydrobiopterin administration during lung allograft reperfusion may reduce posttransplantation lung edema and oxygen-derived free radical injury in the graft. This effect is mediated by local enhancement of the nitric oxide/cyclic guanosine monophosphate pathway. (J Thorac Cardiovasc Surg 1999;118: 726-32)

Levels of antibodies to endotoxin and cytokine release in patients with severe trauma: does posttraumatic dysergy contribute to organ failure?

We conducted a prospective study in patients with multiple injuries investigating the time course of trauma-related changes of systemic immunologic defense mechanisms. Patients with multiple injuries with Injury Severity Scores of more than 20 were included if they survived for more than 4 days after injury. Further inclusion criteria were no local or systemic infection (pneumonia, sepsis, soft-tissue infection, acquired immunodeficiency syndrome, tuberculosis, etc.) at the time of injury and no history of liver disease, bowel disease, or abdominal surgery. Serum endotoxin levels were measured from peripheral venous blood, as were the immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies against lipid A and against the core polysaccharide of endotoxin (lipopolysaccharide [LPS]), during the course of intensive care management. Serial central venous levels of interleukin-6 were determined as a marker of the inflammatory response. The patients were grouped according to their survival, with the survivors belonging to group S (48 patients) and the nonsurvivors belonging to group N (16 patients). The time of death for the nonsurvivors was between days 10 and 32 after the initial trauma. Thirteen of these patients (81%) died of multiple organ failure between days 12 and 17, two died of head trauma, and one died of sepsis. In patients who died of multiple organ failure, a significantly lower production of the IgM and IgG antibodies (AB) against lipid A and LPS was found before death (lipid A IgM-AB, day 11: group N, 29 +/- 11 U/mL; group S, 106 +/- 16 U/mL; p = 0.008; lipid A IgG-AB, day 11: group N, 18 +/- 9 U/mL; group S, 57 +/- 18 U/mL; p = 0.007; LPS IgM-AB, day 11: group N, 36 +/- 14 U/mL; group S, 122 +/- 23 U/mL; p = 0.009; LPS IgG-AB, day 11: group N, 17 +/- 12 U/mL; group S, 56 +/- 19 U/mL; p = 0.03). Interleukin-6 levels were significantly increased in the nonsurvivors (day 1: group N, 1,095 +/- 112 pg/mL; group S, 393 +/- 67 U/L; p = 0.008). In patients who died of severe trauma and in whom the cause of death was multiple organ failure, a significantly lower production of antiendotoxin antibodies was measured shortly before death. An insufficient immune defense (dysergy) may be involved in the pathomechanisms leading to the development of organ dysfunction.

Coagulatory response after femoral instrumentation after severe trauma in sheep.

Pulmonary complications after intramedullary femoral nailing have been attributed to bone marrow fat embolization and a variety of cascade effects. We investigated whether the coagulatory response after intramedullary femoral nailing in merino sheep is altered after severe trauma. Adult merino sheep were submitted to hemorrhagic shock (2 hours, 50 mm Hg) and unilateral lung contusion. After recovery (day 3 of the study), reamed femoral intramedullary nailing (RFN), unreamed femoral intramedullary nailing (UFN), or plate osteosynthesis of the femur (P) was performed. Pulmonary artery pressure, central venous levels of factor V, protein C, antithrombin III, and fibrinogen, were determined. At 1 and 3 days before and after femur instrumentation, pulmonary capillary permeability was assessed on the basis of the comparative albumin content in bronchoalveolar lavage fluid. Group RFN, n=8; group UFN, n=7; group P, n=6. A significant (p < 0.05) postoperative increase in the relative albumin content in terms of the BAL/plasma albumin ratio was measured in group RFN (day 3 preoperatively: 0.38+/-0.05 day 3 postoperatively: 0.53+/-0.06, p < 0.05 (RFN vs. P), which contrasted with group UFN (day 3 preoperatively: 0.44+/-0.09, day 3 postoperatively: 0.46+/-0.09, no significant difference). This evidence of increased pulmonary permeability occurred in association with evidence of increased activation of coagulation factors (data presented as percentage of day 3 preoperative baseline values). The data for fibrinogen (15 min postoperatively) is as follows: group RFN, 74+/-9% (p < 0.05 vs. P); group UFN, 83+/-8% (not significant); group P, 98+/-6%. The data for antithrombin III (15 min. postoperatively) is as follows: group RFN, 72+/-6% (p < 0.05 vs. P); group UFN, 79+/-8% (not significant); group P, 92+/-8% (not significant). After severe trauma, an increase of pulmonary permeability after reamed femoral nailing was associated with increased consumption of coagulation factors. After unreamed nailing, a similar trend was apparent, but this was not found to be statistically significant. These data provide support for the theory that after severe trauma, unreamed femoral nailing reduces but does not abolish pulmonary sequelae when compared with reamed femoral nailing.

Neuronal and adrenal enkephalins and catecholamines in response to acute CNS ischemia and reserpine in pig

Co-storage of enkephalins and catecholamines in coronary artery, mesenteric artery and vein, middle cerebral artery, vas deferens and adrenal medulla was studied in domestic pig ( Sus scrofa). Responses to acute CNS ischemia were correlated with time to peak plasma levels of central venous and adrenal vein outflow samples in controls, during reserpine treatment and after drug withdrawal. Endogenous enkephalins are co-stored in chromaffin granules of adrenal epinephrine-type cells and large dense cored vesicles of noradrenergic terminals. After a lag period, reserpine at near ‘therapeutic’ doses caused an apparent induction of opioid peptide precursor synthesis accompanied by processing to enkephalins in adrenal medulla up to 8-fold by 30 days and in mesenteric vein up to 4.5-fold by 14 days. Upon 14 days recovery from reserpine, elevated adrenal enkephalins were maintained and depleted catecholamines were largely replenished. Acute CNS ischemia produced rises in MAP (approx. 80 mmHg), marked net depletions of noradrenergic enkephalin stores, and net increases in adrenal vein outflow and central venous levels of enkephalins and catecholamines. Noradrenergic terminals contributed significantly to circulating enkephalins as well as norepinephrine. Reserpine for 7 days nearly abolished all tested responses to acute CNS ischemia, but immediate net 200–;400% elevations of endogenous enkephalin stores occurred in coronary artery and mesenteric artery and vein (apparent processing of reserpine-induced neuronal precursor stores). Thus, induction of new synthesis of precursor opioid peptides by reserpine, with or without parallel processing to enkephalins, occurs in noradrenergic terminals in many tissues. All effects of reserpine on endogenous enkephalins implicate a central mechanism to inhibit sympathoadrenal outflow to the periphery. At 14 days recovery from reserpine, when near normal cardiovascular responses to acute CNS ischemia were regained, there was increased net release of the elevated adrenal enkephalins, exaggerated peak plasma enkephalin concentrations, but only minimal depletions of enkephalins from noradrenergic terminals.

Factors affecting the formation of chlorotrifluoroethane and chlorodifluoroethylene from halothane.

Since CF3CH2Cl and CF2CHCl are probably the products of reactive intermediates formed during the reductive metabolism of halothane (CF3CHClBr), factors affecting their in vitro and in vivo formation were investigated. In vitro studies with rat hepatic microsomes showed that CF3CH2Cl and CF2CHCl are produced by cytochrome P-450 mediated reductive pathways which were inhibited by the presence of CO. Under conditions of exposure known to promote halothane hepatotoxicity in phenobarbital treated rats (1 per cent halothane, 14 per cent oxygen), the hepatic and blood concentrations of the volatile metabolites were enhanced. Central venous levels of the volatile metabolites were much higher than he concentration in peripheral vessels. The CF3CH2Cl/CF2CHCl ratio in blood was approximately three, whereas the ratio in vitro was almost unity. Liver levels of the two volatile metabolites greatly exceeded the blood levels, but interestingly they were present in equivalent concentrations. The differences in the ratio of CF3CH2Cl to CF2CHCl may be explained by the fact that CF2CHCl is further degraded under oxidative conditions, whereas CF3CH2Cl appears relatively stable. Measurement of these metabolic products in patients undergoing halothane anesthesia may permit rapid detection of an unusually high level of halothane biotransformation along its hepatotoxic pathway.