Comparison of Hydromorphone versus Fentanyl-based Sedation in Extracorporeal Membrane Oxygenation: A Propensity-Matched Analysis.

INTRODUCTION: Data comparing sedatives in patients receiving extracorporeal membrane oxygenation (ECMO) are sparse. However, it is known that the ECMO circuit alters the pharmacokinetic properties of medications via drug sequestration of lipophilic agents and increased volume of distribution. OBJECTIVES: This study evaluated the difference in days alive without delirium or coma and the sedative requirements in patients receiving fentanyl versus hydromorphone in ECMO patients. METHODS: This single-center retrospective observational study evaluated adults receiving ECMO for more than 48 hours and continuous infusion of either fentanyl or hydromorphone for at least 6 hours. Of 148 patients evaluated, 88 received fentanyl and 60 received hydromorphone continuous infusion sedation. Outcomes included delirium-free and coma-free (DFCF) days, narcotic use, and sedative use. MAIN RESULTS: There was an increase in the number of DFCF days in the hydromorphone group at day 7 (p=0.07) and day 14 (p=0.08) and a significant reduction in daily fentanyl equivalent exposure. Propensity score matching yielded 54 matched pairs. An 11.1% increase was observed in the proportion of ECMO days alive without delirium or coma in the hydromorphone group at 7 days (53.2% vs 42.1%, p=0.006). Patients in the hydromorphone group received significantly fewer narcotics with a median of 555 µg (interquartile range [IQR] 287-905 µg) of fentanyl equivalents per day compared with 2291 µg (IQR 1053-4023 µg) in the fentanyl group (p<0.005). CONCLUSION: The use of hydromorphone-based sedation in ECMO patients resulted in more days alive without delirium or coma while significantly reducing narcotic requirements.

Ethics roundtable debate: is a physician-patient confidentiality relationship subservient to a greater good?

Is a health care provider's most proximal obligation to individuals or society as a whole? Our International panel of critical care providers grapple over the issue of whether patient-physician confidentiality exists as an open ended ideal it should be subservient to a greater good.

Glucose, insulin and potassium (GIK) during reperfusion mediates improved myocardial bioenergetics.

Previous studies suggest glucose, insulin and potassium (GIK) infusion during ischemia reduces infarct size and improves post-ischemic myocardial function in acute myocardial infarction and following surgical revascularization of the heart. The potential use of GIK when given only during reperfusion after a period of global ischemia, as might occur during cardiac arrest, is unclear. To test the hypothesis that GIK reperfusion improves post-ischemic myocardial bioenergetics and function, we utilized a perfused heart model. Hearts from Sprague-Dawley rats (350-450 g) were perfused at 85 mmHg with oxygenated Krebs-Henseleit bicarbonate containing 5.5 mM glucose and 0.2 mM octanoic acid. Following 20 min of global ischemia, hearts were reperfused for 30 min with original solution (control) or GIK in two different doses (10 or 20 mM glucose each with insulin 10 U/l and K(+) 7 meq/l). Hearts perfused with GIK solutions had significantly higher ATP, creatine phosphate, energy charge, and NADP(+) and lower AMP and inosine levels compared with control after 30 min of reperfusion. Hearts reperfused with GIK had significantly higher developed pressure and higher dP/dt than control reperfused hearts. Reperfusion with GIK improved post-ischemic recovery of both contractile function and the myocardial bioenergetic state. GIK may be a viable adjunctive reperfusion therapy following the global ischemia of cardiac arrest to improve post-resuscitation cardiac dysfunction.

The relationship of intraocular pressure to intracranial pressure.

STUDY OBJECTIVE: The early detection of intracranial hypertension can lead to timely medical and neurosurgical intervention, preventing brain herniation and death. In this investigation, we hypothesize that an increase in intracranial pressure can be detected by an increase in intraocular pressure using noninvasive existing technology, the handheld tonometer. METHODS: This was a prospective observational pilot study conducted at a community hospital. Admitted patients with an invasive intracranial pressure monitor were solicited for participation. Patients were excluded if they had known glaucoma or had sufficient ocular or facial trauma that precluded intraocular pressure determination. Simultaneous measurements of intracranial and intraocular pressure were recorded. RESULTS: Twenty-seven patients were enrolled, and 76 individual measurements were performed. All patients with an abnormal intracranial pressure had an abnormal intraocular pressure; similarly, all patients with a normal intracranial pressure had a normal intraocular pressure (sensitivity 1.00, 95% confidence interval 0.86 to 1.0; specificity 1.0, 95% confidence interval 0.93 to 1.0) CONCLUSION: Abnormal intraocular pressure as measured with the handheld tonometer is an excellent indicator of abnormal intracranial pressure in patients with known intracranial pathology.

Initial experience with single cannulation for venovenous extracorporeal oxygenation in adults.

PURPOSE: Historically, venovenous extracorporeal membrane oxygenation has required dual cannulation. A single-venous cannulation strategy may facilitate implantation and patient mobilization. Here we present our early experience with a single cannulation technique. DESCRIPTION: Review of venovenous extracorporeal membrane oxygenation support using internal jugular vein insertion of the Avalon elite bicaval dual lumen catheter (Avalon Laboratories, Rancho Dominguez, CA) in 11 consecutive patients with severe respiratory failure. EVALUATION: Adequate oxygenation was obtained in all patients: 115 mm Hg PaO(2) (median), 53 to 401 mm Hg (range). Median time of support was 78 hours (range, 3 to 267 hours). No mortality was directly related to the cannulation strategy. There were three nonfatal cannulation-related events. Two patients had proximal cannula displacement requiring repositioning. One patient suffered an acute thrombosis of the cannula. CONCLUSIONS: Our series supports single-venous cannulation in venovenous extracorporeal membrane oxygenation as a promising technique. It may be an excellent alternative to current cannulation strategies in patients requiring prolonged support and specifically for those considered for a bridge-to-lung transplantation.

Reactive oxygen species generated during myocardial ischemia enable energetic recovery during reperfusion.

We studied the differences between the functional and bioenergetic effects of antioxidants (AOX) administered before or after myocardial ischemia. Sprague-Dawley rat hearts were perfused with a modified Krebs-Henseleit solution and bubbled with 95% O(2)-5% CO(2). The protocol consisted of 10 min of baseline perfusion, 20 min of global ischemia, and 30 min of reperfusion. An AOX, either 1,2-dihydroxybenzene-3,5-disulfonate (Tiron), a superoxide scavenger, or N-acetyl-L-cysteine, was infused during either baseline or reperfusion. An additional group received deferoxamine as a bolus before ischemia. Hearts were freeze-clamped at baseline, at end of ischemia, and at end of reperfusion for analysis of high-energy phosphates. All AOX, when given before ischemia, inhibited recovery of ATP compared with controls. Both Tiron and deferoxamine also inhibited recovery of phosphocreatine. AOX given before ischemia decreased the efficiency of contraction during reperfusion compared with controls. All of the changes in energetics and efficiency brought on by preischemic AOX treatment could be blocked by a preconditioning stimulus. This suggests that reactive oxygen species, which are generated during ischemia, enhance bioenergetic recovery by increasing the efficiency of contraction.

Postischemic inotropic support of the dysfunctional heart.

OBJECTIVE: To determine relative adenine nucleotide regeneration and improvement in left ventricular (LV) function using three commonly used adrenergic agents--epinephrine, dobutamine, and phenylephrine---during reperfusion after a period of global ischemia. After initial resuscitation from cardiac arrest, adrenergic agents are frequently required to support postischemic LV dysfunction. However, the relative effectiveness and associated bioenergetic changes associated with these agents in the postischemic heart are unclear. DESIGN: Prospective, controlled laboratory study. SETTING: University research laboratory. SUBJECTS: Isolated, perfused Sprague-Dawley rat hearts. INTERVENTIONS: After 20 mins of global ischemia, isolated rat hearts were reperfused for 30 mins with Krebs-Henseleit solution alone (control, n = 8), or with the addition of equipotent doses of epinephrine 1 microM (n = 8), dobutamine 0.3 microM (n = 8), or phenylephrine 50 microM (n = 8). In a second experiment, an alpha-1 antagonist, prazosin was given with phenylephrine to block the presumed alpha-1 agonist effect of phenylephrine. MEASUREMENTS AND MAIN RESULTS: A constant volume balloon was placed in the left ventricle to measure LV pressure and derived parameters of LV function. Adenine nucleotide concentrations were derived at various time points using high-performance liquid chromatography. During reperfusion, the phenylephrine group had significant improvement in LV function and cardiac efficiency in contrast to epinephrine and dobutamine. Total adenine nucleotides tended to be highest in the phenylephrine group with significant increases in adenosine diphosphate and adenosine monophosphate and no significant loss of adenosine triphosphate. The phenylephrine-induced increase in heart rate and developed pressure could be blocked with an alpha-1 antagonist, prazosin. CONCLUSIONS: In the isolated reperfused heart, phenylephrine, mediated by alpha-1 agonism, significantly improves postischemic LV dysfunction without worsening the overall myocardial metabolic state.

Low flow after global ischemia to improve postischemic myocardial function and bioenergetics.

OBJECTIVE: In this study, we test the hypothesis that a period of low flow perfusion before full reperfusion improves ventricular function and bioenergetics. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory. SUBJECTS: Sprague-Dawley rats. INTERVENTIONS: Hearts were perfused with Krebs-Henseleit buffer at 85 mm Hg. The protocol consisted of 10 mins of baseline flow, 15 mins of global ischemia, 5 mins of low flow ischemia, and 30 mins of reperfusion. Groups received 10% or 1% of baseline flow during the low flow period. A control group received 0% low flow (20 mins of global ischemia). MEASUREMENTS AND MAIN RESULTS: Left ventricular function was continuously measured. Hearts were freeze-clamped at various time points, and metabolites were measured. At 10% flow, following global ischemia, both left ventricular function and bioenergetics improved compared with 0% flow and 1% flow. At 1% flow, no changes in function were seen and adenosine 5'-triphosphate concentrations decreased during reperfusion, compared with no flow (9.4 +/- 1.0 vs. 13.2 +/- 1.0 micromol/g of dry weight, p <.01). CONCLUSIONS: Following global ischemia but before full reperfusion, a period of low flow improves postischemic myocardial function and energetic recovery, only if a certain level of low flow is met. Very low flow may further reduce bioenergetic recovery without improvement in postischemic function, compared with continuous global ischemia.