GI complications in patients receiving mechanical ventilation.

Commercially available bupivacaine is an equimolar mixture of R(+)-and S(-)-bupivacaine. S(-)-bupivacaine (i.e., levobupivacaine) is currently undergoing preclinical evaluation. Cross-over studies with IV levobupivacaine and bupivacaine were conducted in two groups of seven conscious sheep. Doses we

Cardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine in sheep.

Most of the current heart failure (HF) prevention or management programs assume that cardiovascular decompensations are primarily driven by volume overload that result in cardiopulmonary congestion. Subsequently, a centerpiece of HF therapies is decongestion of the cardiovascular system. Diuretic

Role of Volume Redistribution in the Congestion of Heart Failure.

https://rapm.bmj.com/content/rapm/30/6/553.full.pdf

Acute toxicity of local anesthetics: underlying pharmacokinetic and pharmacodynamic concepts.

Positive pressure ventilation is a radical departure from the physiology of breathing spontaneously. The immediate physiological consequences of positive pressure ventilation such as haemodynamic changes are recognized, studied, and understood. There are other significant physiological interactions which are less obvious, more insidious, and may only produce complications if ventilation is prolonged. The interaction of positive pressure with airway resistance and alveolar compliance affects distribution of gas flow within the lung. The result is a wide range of ventilation efficacy throughout different areas of the lung, but the pressure differentials between alveolus and interstitium also influence capillary perfusion. The hydrostatic forces across the capillaries associated with the effects of raised venous pressures compound these changes resulting in interstitial fluid sequestration. This is increased by impaired lymphatic drainage which is secondary to raised intrathoracic pressure but also influenced by raised central venous pressure. Ventilation and PEEP promulgate further physiological derangement. In theory, avoiding these physiological disturbances in a rested lung may be better for the lung and other organs. An alternative to positive pressure ventilation might be to investigate oxygen supplementation of a physiologically neutral and rested lung. Abandoning heroic ventilation would be a massive departure from current practice but might be a more rationale approach to future practice.

Positive pressure ventilation: what is the real cost?

The effects of intermittent positive pressure ventilation with PEEP on splanchnic circulation and hepatic oxygen supply were studied in six beagles. PEEP of 0, 0.5 and 1.0 kPa (0, 5, 10 cmH2O, PEEP0, PEEP5 and PEEP10, respectively) of 30 min duration was applied in a random sequence. Hepatic arterial blood flow and portal venous blood flow were measured by electromagnetic flow meters. Blood volume changes in the splanchnic area were assessed from hepatic and splenic dimensions determined by sonomicrometry. PEEP5 and PEEP10 were associated with proportional decreases in both hepatic blood flow and cardiac output, while mean arterial pressure remained unchanged. Reflecting the decrease in hepatic blood flow, the hepatic oxygen supply decreased with the level of PEEP, and hepatic venous hemoglobin oxygen saturation was significantly less during PEEP10 (55.1 +/- 14.3%) than during PEEP5 (62.6 +/- 17.4%) and PEEP0 (62.3 +/- 11.9%). Hepatic venous and portal venous pressure increased with the level of PEEP. Hepatic dimensions increased by 7-8% and 16-19% during PEEP5 and PEEP10, respectively, but no significant changes in splenic dimension were observed. We conclude that PEEP5 and PEEP10 are accompanied by a decrease in hepatic blood flow and oxygen supply along with hepatic congestion.

Effects of PEEP on splanchnic hemodynamics and blood volume

Both the capacitance vessels and the resistance vessels of the splanchnic area are innervated by the sympathetic nerve fibers. We investigated the effect of abdominal visceral sympathectomy on splanchnic circulation, and the effect of altered splanchnic circulation on systemic circulation in ten mongrel dogs. Abdominal visceral sympathectomy was induced by coeliac plexus block with 1 ml/kg (body weight) of 1% lidocaine infiltrated around the coeliac artery. Comparison was made with infiltration of physiologic saline of the same volume. The saline infiltration caused no significant changes in the hemodynamic parameters of systemic and splanchnic circulation. Mean arterial pressure decreased significantly from 18.2 +/- 2.0 to 14.4 +/- 1.9 kPa following the coeliac plexus block, with a concomitant decrease in the cardiac index from 2.63 +/- 0.46 to 2.30 +/- 0.54 l X min-1 X m-2, while systemic vascular resistance was unchanged. Portal vein blood flow, hepatic artery blood flow and, therefore, splanchnic blood flow decreased by 8 to 17%. Portal vascular and hepatic artery resistances were not affected by abdominal sympathectomy. It was concluded that the capacitance vessels in splanchnic circulation are dilated during abdominal sympathetic denervation, causing a blood shift from systemic to splanchnic circulation. On the other hand, the resistance vessels in splanchnic circulation are affected little by abdominal visceral sympathectomy.

Splanchnic circulation following coeliac plexus block.

BACKGROUND Although previous studies have shown that bupivacaine produces a dose-dependent vasoconstriction, the possible effects of decreased coronary blood flow on myocardial dysfunction during bupivacaine-induced cardiotoxicity have not been investigated. METHODS We carried out the present study using the in situ beating hearts of six beagles. An autoperfusion circuit was established from the left carotid artery to the anterior descending coronary artery (LAD). Its blood flow (QLAD) was measured with an electromagnetic flow meter, and myocardial oxygen consumption was calculated using Fick's principle. Regional myocardial function (systolic shortening: %SS, post-systolic shortening: %PSS) of the LAD-supplied region was evaluated by the sonomicrometric technique. While saline or bupivacaine (10 micrograms/ml) was continuously infused into the LAD in a crossover design, the effects of a vehicle (baseline), acetylcholine (1 and 3 micrograms/min), nitroglycerin (10 micrograms/min) and adenosine (10 micrograms/min), on coronary haemodynamics and regional myocardial function were evaluated. RESULTS Bupivacaine caused a decrease in QLAD and regional myocardial dysfunction (a decrease in %SS and an increase in %PSS) at the baseline. While acetylcholine and adenosine increased QLAD with intracoronary bupivacaine-infusion, regional myocardial dysfunction was not reversed. There was a positive correlation between regional myocardial oxygen consumption and %SS in the whole study. CONCLUSIONS The results of this study indicate that the decrease in QLAD during bupivacaine-induced myocardial toxicity is not responsible for regional myocardial dysfunction, and, moreover, that it parallels a decrease in myocardial oxygen demand.

Decreased coronary blood flow is not responsible for myocardial dysfunction during bupivacaine‐induced cardiotoxicity

Metoclopramide in a patient with renal failure may be an increased risk of neuroleptic malignant syndrome

Amrinone has been shown to have therapeutic effects on bupivacaine-induced cardiovascular toxicity, but its exact effects on the heart are not well understood. This study evaluated the regional myocardial effect of amrinone on bupivacaine-induced cardiovascular toxicity in in situ beating hearts in 10 dogs using a selective coronary perfusion and sonomicrometry. In the control group, bupivacaine was administered into the left anterior descending coronary artery (LAD) for 15 min at four steps: baseline, step 1, step 2 and step 3, (calculated LAD plasma concentrations; 0, 5, 5 and 10 mu g center dot ml-1, respectively). In the amrinone group, amrinone (5 mu g center dot ml-1) was simultaneously infused at steps 2 and 3 in addition to bupivacaine infusions. Regional myocardial function of the LAD supplied area was evaluated by analysis of the left ventricular pressure-segment length loop. In the control group, systolic shortening decreased from the baseline (10.5 +/- 1.3%, mean +/- SEM) to step 3 (0.1 +/- 1.3%), and post-systolic shortening increased from the baseline (18.0 +/- 3.7%) to step 3 (52.3 +/- 5.5%) dose-dependently. In contrast, with amrinone infusion at steps 2 and 3, both variables returned to near baseline values. These results indicate that amrinone reverses bupivacaine-induced regional myocardial dysfunction.

Y. Fujita

Papers

Effects of PEEP on splanchnic hemodynamics and blood volume

Splanchnic circulation following coeliac plexus block.

Decreased coronary blood flow is not responsible for myocardial dysfunction during bupivacaine‐induced cardiotoxicity

Metoclopramide in a patient with renal failure may be an increased risk of neuroleptic malignant syndrome

Amrinone reverses bupivacaine-induced regional myocardial dysfunction.