Maintain Mean Arterial Pressure Research Articles

E-067 Intra-arterial nicardipine via guide catheter for the treatment of symptomatic vasospasm following aneurysmal subarachnoid hemorrhage

IntroductionDelayed ischemic neurological deficits secondary to cerebral vasospasm is a major cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Nicardipine has previously been used to treat vasospasm utilizing...

Disparity in regional and systemic circulatory capacities: do they affect the regulation of the circulation?

In this review we integrate ideas about regional and systemic circulatory capacities and the balance between skeletal muscle blood flow and cardiac output during heavy exercise in humans. In the first part of the review we discuss issues related to the pumping capacity of the heart and the vasodilator capacity of skeletal muscle. The issue is that skeletal muscle has a vast capacity to vasodilate during exercise [approximately 300 mL (100 g)(-1) min(-1)], but the pumping capacity of the human heart is limited to 20-25 L min(-1) in untrained subjects and approximately 35 L min(-1) in elite endurance athletes. This means that when more than 7-10 kg of muscle is active during heavy exercise, perfusion of the contracting muscles must be limited or mean arterial pressure will fall. In the second part of the review we emphasize that there is an interplay between sympathetic vasoconstriction and metabolic vasodilation that limits blood flow to contracting muscles to maintain mean arterial pressure. Vasoconstriction in larger vessels continues while constriction in smaller vessels is blunted permitting total muscle blood flow to be limited but distributed more optimally. This interplay between sympathetic constriction and metabolic dilation during heavy whole-body exercise is likely responsible for the very high levels of oxygen extraction seen in contracting skeletal muscle. It also explains why infusing vasodilators in the contracting muscles does not increase oxygen uptake in the muscle. Finally, when approximately 80% of cardiac output is directed towards contracting skeletal muscle modest vasoconstriction in the active muscles can evoke marked changes in arterial pressure.

Hypoxemic Versus Normoxemic Reperfusion in a Large Animal Model of Severe Ischemia-Reperfusion Injury

Prior studies have suggested a significant benefit of using deliberate hypoxemia to reperfuse ischemic tissue beds, primarily by reducing free radical injury. We sought to examine the effects of a hypoxemic reperfusion strategy in a large animal model of severe truncal ischemia. Adult swine were subjected to 30 min of supraceliac aortic occlusion and randomized to two groups: normoxemia group (n = 9), with resuscitation at a pO2 >100 mmHg or hypoxemia group (n = 10), with initial resuscitation at a pO2 of 30-50. The two groups were compared using physiologic parameters, fluid and pressor requirements, inflammatory and oxidative markers, and histologic analysis of end-organ injury. All animals developed significant hemodynamic instability immediately upon reperfusion. Average mean arterial pressure at baseline rose significantly after 30 min of cross-clamp (76.8 versus 166.3 mmHg, P < 0.001). Upon reperfusion, all animals required epinephrine and fluids to maintain mean arterial pressure (MAP) greater than 60 mmHg. After stabilization, the two groups were similar in terms of central and pulmonary hemodynamics. The hypoxemic group required more mean total epinephrine (18.35 mg versus 5.28 mg, P < 0.01) with no significant difference in total fluid volume (hypoxemic 9111 ml versus 8420 mL, P = 0.730). The hypoxemic group demonstrated a more severe metabolic acidosis at all time intervals after reperfusion (pH 7.02 versus 7.16 and lactate 17 versus 13, both P < 0.01). There was no difference in malondialdehyde concentration between the two groups, but the hypoxemic group had a higher antioxidant reductive capacity at all intervals after 30 min of reperfusion (0.23 versus 0.27 uM, P = 0.03). While there was significant end-organ damage on pathologic examination of all liver and kidney specimens (mean severity of injury 1.59 and 1.76, respectively, on a scale of 1-3), there was no significant difference between the two groups. A hypoxemic reperfusion strategy in this large animal model failed to demonstrate any significant clinical benefit. Although there was chemical evidence of improved antioxidant capacity with hypoxemia, it was associated with more instability, metabolic and physiologic derangements, and no evidence of end-organ protection.

Hydrocortisone Supplementation Enhances Hemodynamic Stability in Brain-dead Patients

Hemodynamic instability is frequent in brain-dead patients and may result, in part, from absolute or relative adrenal insufficiency. Corticosteroid supplementation is widely used to restore hemodynamic stability in septic shock and to reduce the time of shock resolution. The authors verified that supplementation with hydrocortisone may enhance hemodynamic stability in brain-dead patients. All consecutive brain-dead patients with hypotension requiring vasopressor agents were included in this single-center noninterventional clinical observation study. Assessment of baseline and adrenocorticotropic hormone (ACTH)-stimulated plasma cortisol concentrations was performed. Immediately after, patients were systematically treated with a single intravenous injection of hydrocortisone (50 mg), and norepinephrine administration was adjusted every 15 min to maintain mean arterial pressure between 65 and 90 mmHg. Adrenal insufficiency was defined as baseline plasma cortisol concentration less than 15 microg/dl and/or delta plasma cortisol concentration less than 9 microg/dl. Patients were considered as ACTH responders when delta cortisol concentration was more than 9 microg/dl 30 min after ACTH injection. Among the 31 patients included, the incidence of adrenal insufficiency was 87% [95% CI, 70-96%]. A significant (> or =30%) decrease in norepinephrine dose was obtained 180 min after hydrocortisone injection in 18 (59%) patients, from 0.31 [0.16-0.44] microg . kg(-1) . min(-1) to 0.18 [0.10-0.24] microg . kg(-1) . min(-1) (P < 0.01). The incidence of hemodynamic response was greater in ACTH nonresponders than in ACTH responders: 86% versus 50%, respectively, P < 0.05. Adrenal insufficiency with hemodynamic instability is frequent in brain-dead patients. After ACTH stimulation testing and hydrocortisone infusion, hemodynamic stability is enhanced especially in patients with true adrenal nonfunction.

Renin‐Angiotensin‐Aldosterone System During Extracorporeal Membrane Oxygenation (ECMO) in a Pig Model of Septic Shock

ECMO is used to provide cardiopulmonary support to critically ill patients, but the ability of the renin‐angiotensin‐aldosterone system to function appropriately during ECMO remains unclear. In this study, plasma renin activity (PRA) and aldosterone (ALDO) were compared at baseline and before and after stabilization on veno‐arterial ECMO for 2 hours in anesthetized piglets either during control (n=10) or endotoxin‐induced septic shock (n=9) states. In control piglets, ECMO was able to maintain mean arterial pressure (MAP) at baseline levels and PRA and ALDO remained unchanged. In contrast, endotoxin induced a 46% decrease (p&lt;0.01) in MAP, and while ECMO could maintain flow at this decreased MAP, it did not return MAP to baseline. PRA appropriately increased in response to shock, but ultimately dropped by 54% (p&lt;0.01) in early ECMO. ALDO increased in response to shock, and remained constant during ECMO. There was a strong correlation between PRA and ALDO at baseline (r=0.90, p&lt;0.01) and on ECMO in control piglets (r= 0.70, p&lt;0.01), but septic shock disrupted that relationship. Plasma sodium concentrations increased (p&lt;0.01) from 137 ± 3.3 to 145 ± 0.7 mEq/L in shock, and with sustained ALDO, remained at this elevated level throughout ECMO. Results suggest that ALDO sodium regulating ability remains intact during ECMO but PRA is attenuated during ECMO in the endotoxic shock state.

Intraaortic Balloon Pump Counterpulsation and Cerebral Autoregulation: an observational study

BackgroundThe use of Intra-aortic counterpulsation is a well established supportive therapy for patients in cardiac failure or after cardiac surgery. Blood pressure variations induced by counterpulsation are transmitted to the cerebral arteries, challenging cerebral autoregulatory mechanisms in order to maintain a stable cerebral blood flow. This study aims to assess the effects on cerebral autoregulation and variability of cerebral blood flow due to intra-aortic balloon pump and inflation ratio weaning.MethodsCerebral blood flow was measured using transcranial Doppler, in a convenience sample of twenty patients requiring balloon counterpulsation for refractory cardiogenic shock (N = 7) or a single inotrope to maintain mean arterial pressure following an elective placement of an intra-aortic balloon pump for cardiac surgery (N = 13). Simultaneous blood pressure at the aortic root was recorded via the intra-aortic balloon pump. Cerebral blood flow velocities were recorded for six minute intervals at a 1:1 balloon inflation-ratio (augmentation of all cardiac beats) and during progressive reductions of the inflation-ratio to 1:3 (augmentation of one every third cardiac beat). Real time comparisons of peak cerebral blood flow velocities with systolic blood pressure were performed using cross-correlation analysis. The primary endpoint was assessment of cerebral autoregulation using the time delay between the peak signals for cerebral blood flow velocity and systolic blood pressure, according to established criteria. The variability of cerebral blood flow was also assessed using non-linear statistics.ResultsDuring the 1:1 inflation-ratio, the mean time delay between aortic blood pressure and cerebral blood flow was -0.016 seconds (95% CI: -0.023,-0.011); during 1:3 inflation-ratio mean time delay was significantly longer at -0.010 seconds (95% CI: -0.016, -0.004, P < 0.0001). Finally, upon return to a 1:1 inflation-ratio, time delays recovered to those measured at baseline. During inflation-ratio reduction, cerebral blood flow irregularities reduced over time, whilst cerebral blood flow variability at end-diastole decreased in patients with cardiogenic shock.ConclusionsWeaning counterpulsation from 1:1 to 1:3 inflation ratio leads to a progressive reduction in time delays between systolic blood pressure and peak cerebral blood flow velocities suggesting that although preserved, there is a significant delay in the establishment of cerebral autoregulatory mechanisms. In addition, cerebral blood flow irregularities (i.e. surrogate of flow adaptability) decrease and a loss of cerebral blood flow chaotic pattern occurs during the end-diastolic phase of each beat in patients with cardiogenic shock.

Role of selective V2-receptor-antagonism in septic shock: a randomized, controlled, experimental study

IntroductionV2-receptor (V2R) stimulation potentially aggravates sepsis-induced vasodilation, fluid accumulation and microvascular thrombosis. Therefore, the present study was performed to determine the effects of a first-line therapy with the selective V2R-antagonist (Propionyl1-D-Tyr(Et)2-Val4-Abu6-Arg8,9)-Vasopressin on cardiopulmonary hemodynamics and organ function vs. the mixed V1aR/V2R-agonist arginine vasopressin (AVP) or placebo in an established ovine model of septic shock.MethodsAfter the onset of septic shock, chronically instrumented sheep were randomly assigned to receive first-line treatment with the selective V2R-antagonist (1 μg/kg per hour), AVP (0.05 μg/kg per hour), or normal saline (placebo, each n = 7). In all groups, open-label norepinephrine was additionally titrated up to 1 μg/kg per minute to maintain mean arterial pressure at 70 ± 5 mmHg, if necessary.ResultsCompared to AVP- and placebo-treated animals, the selective V2R-antagonist stabilized cardiopulmonary hemodynamics (mean arterial and pulmonary artery pressure, cardiac index) as effectively and increased intravascular volume as suggested by higher cardiac filling pressures. Furthermore, left ventricular stroke work index was higher in the V2R-antagonist group than in the AVP group. Notably, metabolic (pH, base excess, lactate concentrations), liver (transaminases, bilirubin) and renal (creatinine and blood urea nitrogen plasma levels, urinary output, creatinine clearance) dysfunctions were attenuated by the V2R-antagonist when compared with AVP and placebo. The onset of septic shock was associated with an increase in AVP plasma levels as compared to baseline in all groups. Whereas AVP plasma levels remained constant in the placebo group, infusion of AVP increased AVP plasma levels up to 149 ± 21 pg/mL. Notably, treatment with the selective V2R-antagonist led to a significant decrease of AVP plasma levels as compared to shock time (P < 0.001) and to both other groups (P < 0.05 vs. placebo; P < 0.001 vs. AVP). Immunohistochemical analyses of lung tissue revealed higher hemeoxygenase-1 (vs. placebo) and lower 3-nitrotyrosine concentrations (vs. AVP) in the V2R-antagonist group. In addition, the selective V2R-antagonist slightly prolonged survival (14 ± 1 hour) when compared to AVP (11 ± 1 hour, P = 0.007) and placebo (11 ± 1 hour, P = 0.025).ConclusionsSelective V2R-antagonism may represent an innovative therapeutic approach to attenuate multiple organ dysfunction in early septic shock.

Spectrum of sepsis mediators source control and management of bundles

Sepsis is a modern medicine icon and the onset of organ dysfunction is one of the worst scenario. More than 100 distinct molecules have been proposed as useful biological markers of sepsis. TNF-alpha, IL-6, chemokines and cytokines are considered the first line factors able to drive the dynamic process of sepsis. The PIRO scheme is a new classification of different aspects, used to stage sepsis. Resuscitation bundles must be started within 6 hours of presentation (serum lactate measured; blood cultures obtained before antibiotic therapy; broad-spectrum antibiotics within 3 hours from emergency admission and 1 hour from ICU admission; in case of hypotension and/or lactate higher than 4 mmol/L deliver an initial 20 ml/kg of crystalloid or colloid solution or apply vasopressors for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure above 65 mmHg). A management bundle should be implemented within 24 hour (low-dose steroids administered for septic shock; recombinant human activated protein C; glucose control maintained at less than 8.3 mmol/L; inspiratory plateau pressures maintained at less than 30 cm H2O).

No Evidence for an Enhanced Role of Endothelial Nitric Oxide in the Maintenance of Arterial Blood Pressure in the IUGR Sheep Fetus

The fetus makes a number of physiological adaptations to a restriction of placental substrate supply, including a decrease in body growth and an increase in peripheral vasoconstriction which maintains mean arterial pressure (MAP) and supports a redistribution of cardiac output to key fetal organs. It is not known, however, whether chronic restriction of placental substrate supply results in an enhanced or diminished role for vasodilators such as endothelial nitric oxide in the regulation of MAP. We hypothesised that there is an increased contribution of NO to blood pressure regulation in growth restricted fetuses and that a 2 h infusion of a nitric oxide synthase inhibitor, N(omega)-nitro- l-arginine methyl ester ( l-NAME) would result in an augmented rise in MAP in chronically hypoxemic, placentally restricted (PR, n = 8) fetuses compared to controls (n = 6) in late gestation. There was no difference in the increase in fetal MAP and decrease in HR during l-NAME infusion between Control and PR fetuses. In the PR group, fetuses with lower mean gestational PaO 2 had a lower increase in MAP during l-NAME infusion. Thus we have found no evidence for an enhanced role of NO in the maintenance of MAP in the chronically hypoxemic IUGR fetus.

Controlled hypotension with desflurane combined with esmolol or dexmedetomidine during tympanoplasty in adults: A double-blind, randomized, controlled trial

Background: Controlled hypotension is a technique that is used to limit intraoperative blood loss to provide the best possible surgical field during surgery. Objective: The aim of this double-blind, randomized, controlled study was to compare the effects of desflurane combined with esmolol or dexmedetomidine on the amount of blood in the surgical field, recovery time, and tolerability in adult patients undergoing tympanoplasty. Methods: Turkish patients aged 18 to 60 years, classified as American Society of Anesthesiologists physical status I or II, who were scheduled for tympanoplasty were randomly divided into 2 groups: the esmolol group or the dexmedetomidine group. After the anesthesia induction in the esmolol group, a loading dose of esmolol was infused intravenously over 1 minute at 1 mg/kg, followed by a maintenance rate of 0.4 to 0.8 mg/ kg/h. In the dexmedetomidine group, a loading dose of dexmedetomidine was infused intravenously over 10 minutes at a rate of 1 μg/kg, followed by a maintenance rate of 0.4 to 0.8 μg/kg/h. The infusion rates were then titrated to maintain mean arterial pressure (MAP) of 65 to 75 mm Hg. General anesthesia was maintained with desflurane 4% to 6%. Heart rate (HR) and MAP were recorded during anesthesia. The following 6-point scale was used to assess the amount of bleeding in the operative field: 0 = no bleeding, a virtually bloodless field; 1 = bleeding that was so mild that it was not a surgical nuisance; 2 = moderate bleeding that was a nuisance but did not interfere with accurate dissection; 3 = moderate bleeding that moderately compromised surgical dissection; 4 = bleeding that was heavy but controllable and that significantly interfered with surgical dissection; and 5 = massive bleeding that was uncontrollable and made dissection impossible. Scores ≤2 were considered to be optimal surgical conditions. The sedation score was determined at 15, 30, and 60 minutes after tracheal extubation using the following scale: 1 = anxious, agitated, or restless; 2 = cooperative, oriented, and tranquil; 3 = responsive to commands; 4 = asleep, but with brisk response to light, glabellar tap, or loud auditory stimulus; 5 = asleep, sluggish response to glabellar tap or auditory stimulus; and 6 = asleep, no response. Time to extubation and to total recovery from anesthesia (Aldrete score ≥9 on a scale of 0–10), adverse effects (eg, intraoperative hypotension [blood pressure <65 mm Hg], bradycardia [HR <50 beats/min]), intraoperative fentanyl consumption, and postoperative nausea and vomiting were recorded. Arterial blood gas analysis and kidney and liver function tests were conducted. All patients were evaluated by the same attending surgeon and anesthesiologist, both of whom were blinded to the administered study drugs. Results: Fifty-two consecutive white patients undergoing tympanoplasty were identified. Two patients had to be excluded because of hypertension and 2 refused to participate. Forty-eight patients were equally randomized to either the esmolol group (n = 24 [16 women, 8 men]; mean [SD] age, 38.4 [10.5] years) or the dexmedetomi-dine group (n = 24 [17 women, 7 men]; mean age, 35.5 [14.7] years). Sedation scores were not collected for 1 patient in the esmolol group; therefore, analysis was conducted for 23 patients. The median (range) of the scores for the amount of blood in the surgical field in the esmolol and dexmedetomidine groups was 1 (0–3) and 1 (0–2), respectively ( P = NS). Mean intraoperative fentanyl consumption in the esmolol group was significantly higher than in the dexmedetomidine group (50.0 [3.0] vs 25.0 [2.5] μg/min; P = 0.002). In the esmolol group, the mean times to extubation and to recovery from anesthesia were significantly shorter than those of the dexmedetomidine group (7.0 [1.4] vs 9.1 [1.9] minutes, respectively; 5.9 [2.1] vs 7.9 [2.3] minutes; both, P = 0.001). The mean sedation scores were significantly lower in the esmolol group (n = 23, because of intent-to-treat analysis) compared with the dexmedetomidine group at 15 minutes (2.5 [0.6] vs 3.6 [0.5]; P = 0.001) and 30 minutes (2.6 [0.6] vs 3.3 [0.6]; P = 0.001) postoperatively. No significant differences were found between the study groups in regard to blood urea nitrogen or creatinine concentration, aspartate aminotransferase or alanine aminotransferase activities, pH, partial pressure of carbon dioxide, or bicarbonate, before or after the operation. Conclusions: Both esmolol and dexmedetomidine, combined with desflurane, provided an effective and well-tolerated method of achieving controlled hypotension to limit the amount of blood in the surgical field in these adult patients undergoing tympanoplasty. Esmolol was associated with significantly shorter extubation and recovery times and significantly less postoperative sedation compared with dexmedetomidine.

Partial intravenous anaesthesia in 5 horses using ketamine, lidocaine, medetomidine and halothane

A partial intravenous protocol was used successfully to maintain anaesthesia in 5 healthy horses. Horses were premedicated with acepromazine, romifidine and butorphanol, induced with guaifenesin and ketamine and maintained on a constant rate infusion of lidocaine, ketamine and medetomidine together with halothane inhalation anaesthesia. Mean end-tidal halothane concentration to maintain a surgical plane of anaesthesia was 0.8 +/- 0.2%. Mean dobutamine requirement to maintain mean arterial pressure above 9.31 kPa was 0.42 +/- 0.3 microg/kg/min. The administration of relatively low doses of lidocaine, ketamine and medetomidine together with halothane resulted in haemodynamically stable anaesthesia, followed by smooth recovery.

Vasopressin decreases intestinal mucosal perfusion: a clinical study on cardiac surgery patients in vasodilatory shock

Low to moderate doses of vasopressin have been used in the treatment of cathecholamine-dependent vasodilatory shock in sepsis or after cardiac surgery. We evaluated the effects of vasopressin on jejunal mucosal perfusion, gastric-arterial pCO2 gradient and the global splanchnic oxygen demand/supply relationship in patients with vasodilatory shock after cardiac surgery. Eight mechanically ventilated patients, dependent on norepinephrine to maintain mean arterial pressure (MAP) > or = 60 mmHg because of septic/post-cardiotomy vasodilatory shock and multiple organ failure after cardiac surgery, were included. Vasopressin was sequentially infused at 1.2, 2.4 and 4.8 U/h for 30-min periods. Norepinephrine was simultaneously decreased to maintain MAP at 75 mmHg. At each infusion rate of vasopressin, data on systemic hemodynamics, jejunal mucosal perfusion, jejunal mucosal hematocrit and red blood cell velocity (laser Doppler flowmetry) as well as gastric-arterial pCO2 gradient (gastric tonometry) and splanchnic oxygen and lactate extraction (hepatic vein catheter) were obtained. The cardiac index, stroke volume index and systemic oxygen delivery decreased and systemic vascular resistance and systemic oxygen extraction increased significantly, while the heart rate or global oxygen consumption did not change with increasing vasopressin dose. Jejunal mucosal perfusion decreased and the arterial-gastric-mucosal pCO2 gradient increased, while splanchnic oxygen or lactate extraction or mixed venous-hepatic venous oxygen saturation gradient were not affected by increasing infusion rates of vasopressin. Infusion of low to moderate doses of vasopressin in patients with norepinephrine-dependent vasodilatory shock after cardiac surgery induces an intestinal and gastric mucosal vasoconstriction.

Clinical research of reptilase combined with hypervolemic hemodilufion and controlled hypoteusion used in tumor surgery

Objective To investigate the safety and efficacy of reptilase combined with hypervolemic hemodilution and coutrolled hypotension used in tumor surgery. Methods 60 ASA Ⅰ - Ⅱ selected patients of tumor surgery were randomly allocated to three groups, group A: reptilase 2 000 U introvenous push before operation, 60 g/L HES(15 ml/kg) infused after induction of anesthesia, and nimodipine was used to maintain mean arterial pressure(MAP) between 60 mm Hg-65 mm Hg; group B, nimodipine was used to maintain MAP between 60 mm Hg-65 man Hg; group C, reptilase 2 000 U introvenous push before operation. HR, MAP, CVP, SpO2 and ECG were continuously monitored throughout operation. Arterial and central venous blood samples were taken for determination of Hb, Hct, PLT, FIB, APTT, PT, Posm and LA at T0 (baseline), T1 (onset of operation) , T2 (1 hour after operation) , T3 (completion of operation) respectively. The volume of blood loss and transfusion were recorded during operation in all patients. Results The value of Hb ,Hct in group A was obviously lower than that in goup B and in group C at T1 and the difference reached statistical significance(P 0. 05). The volume of blood loss and blood transfusion in group A were significantly less than that in goup B and C (P < 0.05 or P < 0.01). Conclusion Reptilase combined with hypervolemic hemodilution and controlled hypotensiou used in tumor surgery could effectively decrease the volume of blood loss during operation with relatively stable hemodynamics and mild side effects, and could be generalized in chnical use. Key words: Reptilase; Hemedilution; Controlled hypotensiou; Carcinoma

Renal haemodynamic, microcirculatory, metabolic and histopathological responses to peritonitis-induced septic shock in pigs

IntroductionOur understanding of septic acute kidney injury (AKI) remains incomplete. A fundamental step is the use of animal models designed to meet the criteria of human sepsis. Therefore, we dynamically assessed renal haemodynamic, microvascular and metabolic responses to, and ultrastructural sequelae of, sepsis in a porcine model of faecal peritonitis-induced progressive hyperdynamic sepsis.MethodsIn eight anaesthetised and mechanically ventilated pigs, faecal peritonitis was induced by inoculating autologous faeces. Six sham-operated animals served as time-matched controls. Noradrenaline was administered to maintain mean arterial pressure (MAP) greater than or equal to 65 mmHg. Before and at 12, 18 and 22 hours of peritonitis systemic haemodynamics, total renal (ultrasound Doppler) and cortex microvascular (laser Doppler) blood flow, oxygen transport and renal venous pressure, acid base balance and lactate/pyruvate ratios were measured. Postmortem histological analysis of kidney tissue was performed.ResultsAll septic pigs developed hyperdynamic shock with AKI as evidenced by a 30% increase in plasma creatinine levels. Kidney blood flow remained well-preserved and renal vascular resistance did not change either. Renal perfusion pressure significantly decreased in the AKI group as a result of gradually increased renal venous pressure. In parallel with a significant decrease in renal cortex microvascular perfusion, progressive renal venous acidosis and an increase in lactate/pyruvate ratio developed, while renal oxygen consumption remained unchanged. Renal histology revealed only subtle changes without signs of acute tubular necrosis.ConclusionThe results of this experimental study argue against the concept of renal vasoconstriction and tubular necrosis as physiological and morphological substrates of early septic AKI. Renal venous congestion might be a hidden and clinically unrecognised contributor to the development of kidney dysfunction.

Non-smokers are more prone to pulmonary oedema than smokers during acute coronary syndrome

Acute coronary syndrome (ACS) patients are prone to develop pulmonary oedema with varied degree of hypoxaemia. The aim was to compare the risk for pulmonary oedema and related complications during ACS amongst non-smokers vs. smokers. Prospective, observational study was performed in consecutive 68 patients presenting with ACS. They were divided into two groups; group 1 (n = 33) non-smokers and group 2 (n = 35) chronic smokers. Standard conservative treatment was given to maintain mean arterial pressure >or= 60 mmHg, oxygen saturation > 95%. The bedside chest x-ray was graded for Battler grading (0-4) for pulmonary oedema. All patients were evaluated for troponin, serial creatinine kinase, echocardiography, arterial blood gas, renal function and correlated with inotropes requirement, active respiratory support, coronary care unit (CCU) stay and hospital outcome. Patients in both the groups had similar cardiac involvement for cardiothoracic ratio, troponin, ejection fraction and creatinine kinase muscle and brain (CK-MB). The bedside chest x-ray revealed significant (p < 0.05) lung oedema grades (3 and 4) in 60% non-smokers (group 1) vs. smokers (11%). These patients (group 1) also presented with significant (p < 0.001) hypoxaemia (lower PaO(2)/FiO(2)-201 +/- 44), metabolic acidosis (higher lactate; 2.1 +/- 0.72 mmol/l, base deficit; -5.1 +/- 4.8) and hypocarbia (28 +/- 2.9 mmHg) than smokers (group 2). The risk estimates for active respiratory support (OR =1.716) and inotrope use (OR = 1.836) was three times higher in non-smokers than smokers. The higher degree of pulmonary oedema and hypoxemia probably contributed to poor short-term outcome in non-smokers than smokers. It would be important to recognise and treat hypoxaemia in non-smokers during ACS.

Effects of short-term simultaneous infusion of dobutamine and terlipressin in patients with septic shock: the DOBUPRESS study

BackgroundTerlipressin bolus infusion may reduce cardiac output and global oxygen supply. The present study was designed to determine whether dobutamine may counterbalance the terlipressin-induced depression in mixed-venous oxygen saturation (Svo2) in patients with catecholamine-dependent septic shock. MethodsProspective, randomized, controlled study performed in a university hospital intensive care unit. Septic shock patients requiring a continuous infusion of norepinephrine (0.9 μg kg−1 min−1) to maintain mean arterial pressure (MAP) at 70 (sd 5) mm Hg were randomly allocated to be treated either with (i) sole norepinephrine infusion (control, n=20), (ii) a single dose of terlipressin 1 mg (n=19), or (iii) a single dose of terlipressin 1 mg followed by dobutamine infusion titrated to reverse the anticipated reduction in Svo2 (n=20). Systemic, pulmonary, and regional haemodynamic variables were obtained at baseline and after 2 and 4 h. Laboratory surrogate markers of organ (dys)function were tested at baseline and after 12 and 24 h. ResultsTerlipressin (with and without dobutamine) infusion preserved MAP at 70 (5) mm Hg, while allowing to reduce norepinephrine requirements to 0.17 (0.2) and 0.2 (0.2) μg kg−1 min−1, respectively [vs1.4 (0.3) μg kg−1 min−1 in controls at 4 h; each P<0.001]. The terlipressin-linked decrease in Svo2 was reversed by dobutamine at a mean dose of 20 (8) μg kg−1 min−1 [Svo2 at 4 h: 59 (11)% vs 69 (12)%, P=0.028]. ConclusionsIn human catecholamine-dependent septic shock, terlipressin (with and without concomitant dobutamine infusion) increases MAP and markedly reduces norepinephrine requirements. Although no adverse events were noticed in the present study, potential benefits of increasing Svo2 after terlipressin bolus infusion need to be weighted against the risk of cardiovascular complications resulting from high-dose dobutamine.

Methylene Blue in the Treatment of Vasoplegia Following Severe Burns

Vasoplegia resulting from severe burns may persist despite adequate fluid resuscitation and treatment with norepinephrine (NE), vasopressin (VP), and steroids. The adenylate cyclase inhibitor methylene blue (MB), currently used in the burn patient to treat methemoglobinemia, has been used to treat vasoplegia after cardiopulmonary bypass. We report the case of MB infusion in two burn patients refractory to NE. The patients had severe burns, 95 and 80% TBSA not responding to conventional treatment. Fluid requirements were estimated according to Parkland formula and then to maintain a urinary output of 30-50 ml/hr. Patient #1, 95% TBSA, was adrenally insufficient and was receiving steroids according to the Annane protocol, as well as VP at 0.2 U/min. His NE requirements were 55 mcg/kg/min. Patient #2, 80% TBSA, was receiving 20 mcg/kg/min of NE. Circulatory failure was defined as inability to maintain mean arterial pressure >70 mm Hg. Hemodynamic and physiologic parameters were measured before and after infusion of a single dose of 2 mg/kg of MB. Both patients showed dramatic improvements in their shock after MB. Patient #1 had an initial reaction within 30 minutes and reached peak effect at 1 hour. His NE requirements decreased to 0.2 mcg/kg/min and VP decreased to 0.04 U/min. Patient #2 showed effects within 15 minutes of the infusion and by 2 hours the NE was stopped. No adverse side effects were noted in either of the two patients. The fact that MB successfully reversed refractory vasoplegia after severe burns suggests a new tool for treating a small subgroup of patients who exhibit persistent vasoplegia from their burn injury. A controlled randomized trial is needed to test its effects on a large number of patients and graft survival.

Effect of remifentanil on postoperative pain in gynecologic surgery with sevoflurane anesthesia

Background: Rapid development of acute opioid tolerance and hyperalgesia is well established in animal studies and is more likely to occur with large doses of short-acting drugs. Several experimental and clinical studies of varied design that have been conducted in humans comparing remifentanil with other routinely used anesthetics or placebo preparations have produced conflicting results. The aim of this study was to investigate whether remifentanil had any impact on postoperative pain after gynecologic surgery. Methods: Sixty patients undergoing gynecological surgery were randomly allocated into three groups (each n=20): N group with normal saline, L group with target-controlled infusion (TCI) of 1 ng/ml remifentanil, and H group with TCI of 3 ng/ml remifentanil. All patients were anesthetized with sevoflurane to maintain mean arterial pressure within 20% of basal values. Thirty minutes before the end of surgery, patients received morphine sulfate through a patient-controlled infusion device. Pain scores, sedation scores, and analgesic requirements were recorded for 48 hours postoperatively. Results: The mean remifentanil infusion dose of the H group was significantly higher than that of the L group. The VAS scores of the L and H groups were significantly higher than those of the N group only at the postanesthetic care unit and not at the ward. Conclusions: Intraoperative use of remifentanil with sevoflurane may be related to increased postoperative pain during early postanesthetic period. Provision for effective preventive and therapeutic management strategies in case of intraoperative remifentanil use may be reasonable.

Abstract 56: Ventilation Is Necessary During Cardiopulmonary Resuscitation In A Rat Model Of Cardiac Arrest Induced By Airway Obstruction

Recent studies have showed that hypoventilation during cardiopulmonary resuscitation (CPR) improved the rates of return of spontaneous circulation (ROSC) and prognosis. However, there are few studies about the ventilation strategies during CPR in cardiac arrest caused by airway obstruction. To compare the effects of the three ventilation strategies during CPR in an animal model of cardiac arrest induced by airway obstruction, we investigated the rates of ROSC, survival rates, plasma cytokine levels, and lactate levels. thirty-six male Sprague Dawley rats were anesthetized with intraperitoneal injection of pentobarbital. Cardiac arrest was induced by airway obstruction. After 3 minutes of cardiac arrest, animals were randomized to receive one of the three ventilation strategies during CPR (n = 12 per group): normoventiraion (28 breaths/min), hypoventilation (14 breaths/min), or no-ventilation. The rates of chest compression (CC) was 240 –260 compressions/min and the depth of CC adjusted to maintain mean arterial pressure more than 25 mmHg in all groups. After 5 minutes of CPR, epinephrine (0.02 mg/kg) was administered, and all rats were ventilated at the rates of 28 breaths/min in FiO2 1.0. The rates of ROSC were 83%, 58%, 0% for the normoventilation, hypoventilation, and no-ventilation groups, respectively. The PaCO2 levels immediately after ROSC were 74mmHg and 88 mmHg for the normoventilation, and hypoventilation groups, respectively. The increases of plasma cytokine (TNF-a, and IL-6) levels and lactate levels after ROSC in the normoventilation group were significantly less than those in the hypoventilation group. The present study showed that normoventilation during CPR improved the rates of ROSC and the survival rates after ROSC in the animal cardiac arrest model induced by airway obstruction. Moreover, normoventilation attenuated the elevation of cytokine and lactate responses. These findings suggest that ventilation may be necessary during CPR in cardiac arrest caused by airway obstruction.

Thresholded Area Over the Curve of Spectrometric Tissue Oxygen Saturation as an Indicator of Volume Resuscitability in Porcine Hemorrhagic Shock

A rapid, reliable, and noninvasive functional measure of responsiveness to resuscitation in posttraumatic hemorrhagic shock could prove useful in guiding therapy, especially under circumstances such as the battlefield and civilian mass casualties. Tissue oxygen saturation (Sto2) is a promising candidate for this application. We therefore explored the value of peripheral muscle Sto2 in predicting systemic responsiveness to colloid volume resuscitation in a porcine model of hemorrhagic shock. Fourteen isoflurane-anesthetized piglets were subjected to a standardized hemorrhage protocol that maintained mean arterial pressure (MAP) between 30 and 40 mm Hg. Asanguineous resuscitation with a volume of Hextend equal to the total volume bled was initiated when compensation was exhausted (MAP <30 mm Hg). We recorded continuous MAP and Sto2 values, and calculated the contiguous area over the Sto2 curve yet below a given threshold of Sto2 (TAOC) as a function of this threshold before the selected timepoint for timepoints up to 30 minutes before resuscitation. Hemorrhage resulted in significant fluctuations of MAP and high interindividual variability of disease dynamics and outcome: 4 nonsurvivors and 10 survivors at 2 hours postresuscitation. Sto2 measurements reflected hemodynamic conditions in most animals, with a pronounced drop preceding final decompensation in 7 of 14 animals. TAOC discriminated three of four nonresuscitable (nonsurvivor) animals from the survivors, with group differences reaching significance even for the earliest examined timepoint (30 minutes before resuscitation), depending on the choice of TAOC threshold. Sto2 may serve as a marker of decompensation, whereas TAOC, a physiologically motivated correlate of perfusion debt and cumulative hypoperfusion injury, may be a useful early indicator of responsiveness to volume resuscitation in hemorrhagic shock.