The NO donor SIN-1 improves intestinal-arterial P(CO(2)) gap in experimental endotoxemia: an animal study.

BACKGROUND: Dysfunction of the microcirculation is a prominent feature of sepsis and endotoxemia. Recently, it has been shown that microcirculatory alterations are completely reversed by local or systemic application of vasodilators in severely septic patients. Therefore, we investigated the influence of vasodilator therapy on microcirculatory dysfunction of the ileum during endotoxic shock in a prospective, controlled animal study. METHODS: After baseline measurements, shock was induced in 12 domestic pigs by lipopolysaccharide via the mesenteric vein until the mean arterial pressure fell below 60 mmHg. After 30 min in shock, six animals were resuscitated with either fluid alone (control) or fluid and 2 microg/kg/min of the vasodilator 3-morpholino-sydnonimine (SIN-1). The systemic and regional hemodynamics and oxygenation parameters, tonometric ileal P(CO(2)) and microvascular oxygen pressures (muP(O(2))) (by oxygen-dependent Pd-porphyrin phosphorescence) were measured simultaneously. RESULTS: The ileal-arterial P(CO(2)) gap increased during shock and the ileal mucosal and serosal muP(O(2)) decreased concurrently. SIN-1 in addition to fluid resuscitation significantly improved the ileal-arterial P(CO(2)), whereas fluid alone failed to decrease the P(CO(2)) gap. The SIN-1-induced improvement in the P(CO(2)) gap was accompanied by an increase in serosal muP(O(2)) above shock levels. Mucosal muP(O(2)) was resuscitated to baseline levels in both groups. CONCLUSION: The application of the vasodilator SIN-1 in addition to fluid resuscitation improves the ileal-arterial P(CO(2)) gap and mucosal muP(O(2)), together with a moderate increase in serosal muP(O(2)), after endotoxic shock. This finding is consistent with the concept that vasodilators may correct pathologic flow distribution within the intestinal wall.

Effects of dopexamine in a rat model of supracoeliac aortic cross-clamping and declamping.

This experimental study in rats was designed to demonstrate effects of dopexamine (3 microg kg(-1) min(-1), n = 6) or physiologic saline solution (n = 6) on systemic as well as regional perfusion during 30 min of supracoeliac aortic cross-clamping and during 180 min of reperfusion following declamping. Rats were surgically instrumented with arterial, right atrial and portal venous catheters, ultrasonic flow probes around the abdominal aorta, superior mesenteric and carotid artery, and a paediatric tonometer for intestinal mucosal PCO(2) measurement. During 120 min of reperfusion, fluid resuscitation was titrated to keep abdominal aortic blood flow above 80% of baseline values. We found that during cross-clamping, values of arterial lactate (p = 0.002) and intestinal tonometric PCO(2) (p = 0.018) were higher in the dopexamine group than in the control group.

Predictors of long-term mortality and cardiac events in patients with known or suspected coronary artery disease who survive major non-cardiac surgery.

The aim of this prospective study was to assess predictors of long-term outcome in patients with documented or suspected coronary artery disease who survive major non-cardiac surgery. The impact of patients' comorbidities, pre-operative heart rate variability and postoperative increase in cardiac troponin I on all-cause mortality and major cardiac events within 2 years was explored using multivariable logistic regression. Six of 173 patients died within the first month after surgery and were excluded from the study. Thirty-four of 167 patients (20%) died 1-24 months after surgery. Independent predictors of all-cause mortality were history of congestive heart failure (odds ratio 6.4 [95%, confidence interval 1.7-24]), pre-operatively depressed heart rate variability (odds ratio 6.4 [95%, confidence interval 1.9-21]), and age > 70 years (odds ratio 4.5 [95%, confidence interval 1.2-16]). In contrast, postoperative elevation of cardiac troponin I did not independently predict all-cause mortality or major cardiac events.

Doppler indices of diastolic transmitral flow velocity are invalid indicators of myocardial ischaemia during high-dose dobutamine infusion in anaesthetized patients.

BACKGROUND AND OBJECTIVE: Doppler echocardiography of diastolic transmitral flow velocity is more sensitive for the detection of myocardial ischaemia in awake patients than echocardiographic analysis of systolic wall motion. However, its diagnostic value in anaesthetized patients is unknown. METHODS: Doppler indices of diastolic transmitral flow velocity previously found to be highly sensitive for detecting ischaemia in awake patients were studied in 72 anaesthetized patients with documented coronary artery disease undergoing dobutamine stress echocardiography. These Doppler indices were compared with standard echocardiographic and electrocardiographic criteria for ischaemia. RESULTS: Sixty-five patients showed evidence of ischaemia by standard echocardiographic and/or electrocardiographic criteria, and seven patients did not. Regardless of evidence of ischaemia by standard criteria, the Doppler indices changed similarly in both groups. Accordingly, only a minority of anaesthetized patients displayed the changes in Doppler indices of diastolic transmitral flow previously suggested to be sensitive for detecting ischaemia. CONCLUSIONS: The results do not confirm the diagnostic value of Doppler echocardiography of diastolic transmitral flow velocity for detecting ischaemia in anaesthetized patients undergoing dobutamine stress echocardiography during positive-pressure ventilation of the lungs.

Perioperative management of a child with very-long-chain acyl-coenzyme A dehydrogenase deficiency.

Very-long-chain acyl-coenzyme A dehydrogenase deficiency is an inborn error of fatty acid metabolism. The clinical presentation of this disease in children is either a severe form with onset of symptoms in the first months of life, cardiomyopathy, metabolic acidosis, myopathy and a high mortality, or a less severe form manifesting mainly with hypoglycaemia. Perioperative fasting and (even emotional) stress can trigger metabolic decompensation through the altered metabolism of endogenous fatty acids resulting in hypoglycaemia, acute cardiac and hepatic dysfunction and rhabdomyolysis. We report the perioperative management of a 9-year-old boy suffering from the severe form of this disease who underwent circumcision. Metabolism was kept stable in this child by using a glucose--electrolyte infusion throughout the perioperative period to avoid the biochemical consequences of fasting and a benzodiazepine--opioid technique combined with regional anaesthesia to minimize the stress response. Considering reports about a possible interference of propofol with fatty acid oxidation and to avoid the unnecessary administration of fatty acids, propofol should not be used in these patients.

[Volume therapy in hypotensive trauma patients]. / Volumentherapie bei hypotensiven Traumapatienten.

In trauma patients it is mandatory to establish the exact reason for their hypotension. If hypovolaemia is most probably responsible for the hypotension, fluid resuscitation should be initiated. The therapy of choice is infusion of sugarless, isotonic crystalloids with a physiologic serum electrolyte composition. In patients with brain injuries a decrease in serum osmolality is not advisable and hypertonic fluids may therefore be considered. Human albumin preparations are no longer indicated, but synthetic colloids may be an adjunct to a pure crystalloid regime. Hydroxyethyl starch preparations with a molecular weight in the mean range are reasonable choices considering the individual advantages and disadvantages of the various colloids. Larger blood losses must be treated with blood components such as packed red cells, fresh frozen plasma and thrombocyte concentrates as indicated. There are no widely accepted values for laboratory or monitoring parameters in starting or stopping a given fluid therapy; these values are unquestionably influenced, among other things, by the patient history and the pattern of the injuries. Initial resuscitation (when to start, who should administer the fluid and how much) also remains a focus of heated controversy.

Competence of the internal jugular vein valve is damaged by cannulation and catheterization of the internal jugular vein.

BACKGROUND: Experimental results suggest that the competence of the internal jugular vein (IJV) valve may be damaged when the IJV is cannulated for insertion of a central venous catheter. It has further been hypothesized that the risk of causing incompetence of the proximally located valve might be reduced by using a more distal site for venous cannulation. The present study evaluated these hypotheses in surgical patients. METHODS: Ninety-one patients without preexisting incompetence of the IJV valve were randomly assigned to undergo distal or proximal IJV cannulation (> or = 1 cm above or below the cricoid level, respectively). Color Doppler ultrasound was used to study whether new valvular incompetence was present during Valsalva maneuvers after insertion of a central venous catheter, immediately after removal of the catheter, and, in a subset of patients, several months after catheter removal, when compared with baseline findings before cannulation of the IJV. RESULTS: Incompetence of the IJV valve was frequently induced both by proximal and distal cannulation and catheterization of the IJV. Its incidence was higher after proximal than after distal cannulation (76% vs. 41%; P < 0.01) and tended to be so after removal of the catheter (47% vs. 28%; P = 0.07). Valvular incompetence persisting immediately after removal of the catheter did not recover within 8-27 months in most cases. CONCLUSIONS: Cannulation and catheterization of the IJV may cause persistent incompetence of the IJV valve. Choosing a more distal site for venous cannulation may slightly lower the risk of causing valvular incompetence but does not reliably avoid it.

Supraceliac aortic cross-clamping and declamping. Effects of dopexamine and dopamine on systemic and mesenteric hemodynamics, metabolism and intestinal tonometry in a rat model.

BACKGROUND: The effects of dopexamine and dopamine on mesenteric ischemia during reperfusion following aortic cross-clamping are not known. We determined intramucosal tonometric PCO2 and PCO2 gap using a rat model of supraceliac aortic cross-clamping and declamping. METHODS: Under pentobarbital and fentanyl anesthesia, 24 rats were surgically instrumented with arterial, right atrial, and portal venous catheters, ultrasonic flowprobes for measurements of abdominal aortic, superior mesenteric and carotid artery blood flow, and a pediatric tonometer for intestinal mucosal PCO2 measurements. Rats were randomized to receive a continuous infusion of dopexamine (10 x microg(-1) x kg(-1) x min(-1), n=8), dopamine (10 microg x kg(-1) x min(-1), n=8 ), or physiologic saline (control, n= 8), infused at a rate of 4 ml x kg(-1) x h(-1), administered throughout the experimental protocol. After 30 min of drug infusion, the aorta was cross-clamped at the supraceliac level for 30 min. Reperfusion following declamping was observed for 180 min. RESULTS: Intestinal tonometric PCO2 remained unchanged during drug treatment before aortic cross-clamping, increased similarly in all groups following declamping during early reperfusion, and recovered to baseline within 30 min of reperfusion. Dopexamine treatment was associated with higher lactate levels and increased heart rate (P<0.05) during aortic cross-clamping. CONCLUSIONS: 1) Mesenteric ischemia, determined by intestinal tonometric PCO2 and PCO2 gap, recovers within 30 min of reperfusion following 30 min of aortic cross-clamping irrespective of drug treatment and, 2) dopexamine induced higher lactate levels and increased heart rate during aortic cross-clamping and should be carefully analyzed for potentially adverse effects on cardiac function.

The diagnostic value of Doppler echocardiographic indexes of diastolic filling for detecting demand ischemia in anesthetized patients.

UNLABELLED: In awake patients, Doppler indexes of transmitral flow velocities have been shown to be more sensitive for detection of myocardial ischemia than echocardiographic evaluation of systolic wall-motion. The diagnostic value of these indexes in anesthetized patients is unknown. It might differ from that in awake patients because anesthetics and sympathomimetic drugs, which are commonly used in surgical patients with coronary artery disease (CAD), independently affect transmitral flow velocities. METHODS: Several previously published transmitral Doppler echocardiographic indicators of ischemia (marked decreases in the ratio of peak early [E] to peak atrial [A] filling velocity [E/A], in the ratio of early to atrial time-velocity integral [E(I)/A(I)], in E, in E acceleration, and in total diastolic time-velocity integral) were compared with standard wall-motion analysis and ST-segment analysis during dobutamine stress echocardiography (DSE) in 17 anesthetized patients with CAD and 7 age-matched control patients at low risk of CAD. RESULTS: All patients with CAD but no control patients showed new systolic wall-motion abnormalities and/or ST-segment changes. Decreases of >10% in E/A and E(I)/A(I) were found in 88% and 71% of the patients with CAD and in 71% and 100% of the control patients, respectively. These decreases were found during dobutamine infusion at as low as 10 mcg/kg/min in several control patients. None of the other studied Doppler indexes were found useful to detect ischemia. CONCLUSIONS: Doppler echocardiography of diastolic transmitral flow velocities is of no appreciable diagnostic value for detecting ischemia in anesthetized patients who receive dobutamine at 10-40 mcg/kg/min.

High incidence of intravenous thrombi after short-term central venous catheterization of the internal jugular vein.

STUDY OBJECTIVE: To assess incidence and characteristics of intravenous (i.v.) thrombi associated with short-term central venous catheterization through the internal jugular vein. DESIGN: Prospective clinical study. SETTING: University hospital. PATIENTS: 81 patients undergoing cardiac surgery. INTERVENTIONS: A triple-lumen central venous catheter was inserted into the right internal jugular vein immediately before surgery and removed 3 to 4 days later. Heparin at an i.v. dose of 15,000 IU/24 hours was started 6 hours after surgery and continued until the first postoperative morning, followed by subcutaneous low molecular weight heparin 5,000 IU/day in combination with oral aspirin 100 mg/day. MEASUREMENTS AND MAIN RESULTS: Anatomy of the internal jugular vein and i.v. blood flow were studied using two-dimensional and color Doppler ultrasonography before insertion of the catheter and after its removal. Thrombi were found in 45 patients (56%). Twenty-five of these thrombi (56%) had the shape of a sleeve, and 20 thrombi (44%) were compact. Length of the thrombi was 1.4 +/- 0.8 cm (mean +/- SD). Half of the thrombi floated with venous blood flow and half were stable. Neither impaired venous blood flow nor clinical signs of embolism or sepsis was found. Follow-up studies in eight patients revealed that the thrombi had not disappeared 5 days after removal of the catheter but had become smaller. CONCLUSION: The incidence of i.v. thrombi associated with short-term catheterization of the internal jugular vein was high despite prophylactic anticoagulation. This finding reaffirms the importance of removing central venous catheters as soon as clinically possible. Additional studies using specific outcome tests are needed to thoroughly assess the clinical importance of this finding.

[Perioperative management of patients with arterial hypertension]. / Perioperatives Management von Patienten mit arterieller Hypertonie.

Concomitant arterial hypertension in surgical patients is an indicator of increased risk for peri-operative cardiovascular complications. This review article discusses reasons for the increased risk and gives recommendations for the perioperative management of patients with arterial hypertension. In patients with established anti-hypertensive therapy, it is of greatest importance to continue this therapy perioperatively. In addition, the management of patients with preoperatively elevated arterial blood pressure is addressed, and recommendations are provided as to when it seems safe to go on with surgery and when prudent to delay surgery to control hypertension.

Evaluation of a new self-expandable silicone stent in an experimental tracheal stenosis.

STUDY OBJECTIVES: To assess the usefulness of an animal model for testing new tracheobronchial stents. SETTING: Animal laboratory of a university hospital. ANIMALS AND INTERVENTIONS: In a series with 12 mini-pigs, we induced a stable fibromalacic tracheal stenosis that was 50% to 70% of the normal tracheal diameter. After dilation we inserted a 16 x 40-mm self-expandable silicone stent into the stenotic part of the trachea in 10 of the mini-pigs. Five of the stents had a smooth outer surface, and five had additional silicone retaining spikes. Because of a long stenosis in two of the mini-pigs, two overlapping stents (one smooth and one with spikes) were inserted. MEASUREMENTS AND RESULTS: Stent deployment was successful and resulted in the disappearance of the slight to moderate stridor in all of the mini-pigs. Over a mean (+/- SD) observation period of 24 days (range, 10 to 41 days), all of the mini-pigs redeveloped stridor. Three of them died unexpectedly of suffocation: in all three a smooth stent had migrated, leading to total obstruction of the stenosis. In total, five of the six smooth stents migrated, and only one of the six spiked stents migrated. There was considerable granulation tissue formation at the ends of all of the stents. In the two control mini-pigs, a 12 x 35-mm Dumon stent was inserted. Both Dumon stents migrated, and one of them had considerable granuloma formation at its ends. At the end of the observation period, all stents were removed endoscopically and were found not to have deteriorated over time. CONCLUSIONS: Our model proved to be suitable for the evaluation of the technical aspects of the Polyflex stent. Spikes on the outer stent surface are more effective in preventing migration than smooth-surface stents. Long-term compatibility, however, seems to be difficult to test with our model because both the Polyflex and the Dumon stents had excessive granulation tissue formation at both ends, a factor which--in the case of the Dumon stent--does not occur to such a degree in benign human airway stenoses. Our results indicate a need for prospective long-term studies in benign human airway stenoses.

Systemic and mesenteric hemodynamics, metabolism, and intestinal tonometry in a rat model of supraceliac aortic cross-clamping and declamping.

OBJECTIVE: To describe systemic and mesenteric hemodynamics, metabolism, and intestinal tonometry in a rat model of supraceliac aortic cross-clamping and declamping. DESIGN: Prospective, randomized, experimental study. SETTING: University cardiovascular research laboratory. PARTICIPANTS: Twelve male anesthetized and ventilated Sprague-Dawley rats. INTERVENTION: Supraceliac aortic cross-clamping was performed for 30 minutes, followed by declamping and reperfusion for 180 minutes or sham clamping and sham declamping. MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure; abdominal aortic, superior mesenteric, and carotid artery blood flow; intestinal mucosal tonometry; hemoglobin; lactate; and blood gases were measured before and after 30 minutes of aortic cross-clamping and 15, 30, 60, 120, and 180 minutes after declamping during reperfusion. Aortic cross-clamping induced an increase in mean arterial pressure (117+/-20 mm Hg to 147+/-12 mm Hg), an increase in right atrial hemoglobin saturation(66%+/-11% to 81%+/-6%), an increase in lactate levels (1.7+/-0.7 mmol/L to 4.3+/-1.3 mmol/L), and an increase in tonometric PCO2 (49.6+/-5.0 mm Hg to 75.6+/-8.6 mm Hg). Three hours of reperfusion after declamping resulted in significantly decreased mean arterial pressure (38+/-10 mm Hg); decreased aortic (101+/-12 mL/min/kg to 57+/-32 mL/min/kg), mesenteric (19+/-4 to 13+/-6 mL/min/kg), and carotid (12+/-4 mL/min/kg to 5+/-3 mL/min/ kg) blood flows; and elevated lactate levels (4.2+/-2.0 mmol/L). Tonometric PCO2 had normalized to baseline levels (51.9+/-3.8 mm Hg), but PCO2 gap was significantly higher than in sham clamped rats (17.9+/-7.8 mm Hg v. 7.0+/-2.6 mm Hg). CONCLUSIONS: Hemodynamic and metabolic effects of aortic cross-clamping and declamping known from large animal models are reproducible using a rat model. Intestinal tonometry indicated mesenteric ischemia during aortic cross-clamping, which was reversible to preclamp values within 30 minutes of reperfusion after declamping.

Occlusive mesenteric ischemia and its effects on jejunal intramucosal pH, mesenteric oxygen consumption and oxygen tensions from surfaces of the jejunum in anesthetized pigs.

OBJECTIVE: To investigate the effects of superior mesenteric artery (SMA) flow reduction on the jejunal intramucosal pH (pHi) and to compare these effects with corresponding changes of mesenteric oxygen transport variables and oxygen tensions on the surfaces of the jejunal serosa and mucosa. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: Animal research laboratory. SUBJECTS: 20 domestic pigs. INTERVENTIONS: Mechanical flow reduction in the SMA. The animals were randomized to have an SMA flow of 0%, 25%, 38%, 50% or 100% (control). MEASUREMENTS AND MAIN RESULTS: Measurements (baseline, ischemia, reperfusion) consisted of hemodynamic and oxygen transport variables, SMA blood flow, mesenteric oxygen transport variables, pHi and oxygen tensions of the jejunal serosa and mucosa. Flow reduction in the SMA resulted in a significant decrease of pHi indicating ischemia earlier than mesenteric oxygen transport variables. The relationship between mesenteric oxygen delivery (DO2ms) and pHi during acute ischemia is best described by a sigmoid curve. There was a linear correlation between the changes of the jejunal surface oxygen tensions and pHi due to SMA flow reduction. CONCLUSION: The sigmoid relationship between pHi and DO2ms indicated that pHi is a sensitive parameter for detecting ischemia at 50% of the baseline oxygen delivery and that below 25% there was no further decrease of pHi. In contrast, mesenteric and whole body oxygen transport parameters were not indicative of impaired mucosal oxygen supply.

An experimental comparative study on the characteristics of ventricular fibrillation during cardiac arrest and methoxamine administration.

The effect of a pure alpha-adrenergic agent, methoxamine on ventricular fibrillation (VF) amplitude and the relation between hemodynamic parameters and survival in a rodent cardiopulmonary resuscitation (CPR) model were studied. Our results suggested that: 1) VF amplitude decreased during untreated VF, but it increased during pericardial chest compression: 2) methoxamine significantly increased the mean aortic pressure (MAP) and coronary perfusion pressure (CPP) but not VF amplitude, and the survival also increased due to elevation of CPP; and 3) all surviving animals with successful defibrillation had a higher VF amplitude.

Effect of different drugs on end-tidal carbon dioxide during rodent CPR.

The purpose of this study was to investigate the effect of non-adrenergic agents on cardiopulmonary resuscitation (CPR) and end-tidal CO2 (ETCO2) during CPR in a rodent model. Our results suggested that: 1) coronary perfusion pressure (CPP) after drugs infusion was increased significantly by methoxamine, arginine vasopresin (AVP) and angiotension-II (ANG-II), but not by endothelin-1 (ET-1); 2) ETCO2 prior to defibrillation was decreased significantly by a pure alpha 1 adrenergic agents, methoxamine and were increased significantly by non-adrenergic agents, ANG-II and ET-1 during rodent CPR; 3) a significant positive correlation between ETCO2 and CPP was observed in AVP group, suggesting that AVP have little effect on pulmonary circulation; and 4) methoxamine, AVP and ANG-II have similar effect on resuscitability during rodent CPR.

Decreased left ventricular contractility during porcine endotoxemia is not prevented by ibuprofen.

OBJECTIVE: We investigated whether ibuprofen could prevent early decrease in left ventricular contractility that occurs during porcine endotoxemia. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Adolescent crossbred pigs (n = 28). INTERVENTIONS: Anesthetized pigs were instrumented to measure hemodynamics and left ventricular pressures (using a Millar catheter) and volumes (using a conductance catheter). Pigs were then treated in four groups, according to pretreatment using ibuprofen (15 mg/kg) or saline and subsequent treatment using endotoxin (0111:B4, 50 microg/kg) or saline. MEASUREMENTS AND MAIN RESULTS: Measurements of hemodynamics and left ventricular pressures and volumes were repeated after pretreatment with ibuprofen (or saline in controls), and at hourly intervals for 4 hrs after the start of endotoxin or control saline infusions. Left ventricular contractility was primarily assessed using the slope of the end-systolic pressure-volume relationship. Data were analyzed, using a repeated-measures analysis of variance. The slope of the end-systolic pressure-volume relationship was decreased at 4 hrs by 41 +/- 9% in the saline/endotoxin group (p < .05) and by 36 +/- 14% in the ibuprofen/endotoxin group (p < .05), so that ibuprofen pretreatment had no significant effect on the decrease in left ventricular contractility. Mean arterial pressure decreased in the saline/endotoxin group by 23 +/- 12% at 1 hr (p < .05) and by 35 +/- 12% (p < .05) at 4 hrs. Ibuprofen significantly reduced the decrease in mean arterial pressure (2 +/- 6% increased at 1 hr, and 17 +/- 12% decreased at 4 hrs, both p<.05 compared with saline/endotoxin). Cardiac output increased by 25% (p < .05) in the first hour, but then decreased to be slightly (NS) below baseline at 4 hrs in both endotoxin groups. Mean pulmonary arterial pressure was increased in the saline/endotoxin group by 154 +/- 52% (p < .05) at 30 mins and by 118 +/- 40% (p < .05) at 4 hrs. Ibuprofen prevented the very acute increase in pulmonary arterial pressure (increased by 11 +/- 33% at 30 mins, p < .05 compared with saline/endotoxin) and significantly reduced the pulmonary hypertension at 4 hrs (increased by 70 +/- 25%, p < .05 compared with both baseline and saline/endotoxin). CONCLUSIONS: We conclude that products of the cyclooxygenase pathway do not play a major role in the early decrease in left ventricular contractility after endotoxin. However, ibuprofen may have a role in reducing the other cardiovascular effects of sepsis.