Erica D. Wittwer

β‐Adrenoceptor gene variation and intermediate physiological traits: prediction of distant phenotype

Intermediate physiological phenotype is the genetic and environmental influence on functional physiological characteristics with direct prognostic relevance to distant, more complex phenotypes, such as cardiovascular and metabolic disease. Increasingly available and affordable genotyping techniques have created an explosion of information on candidate gene variation and its relationship to intermediate physiological traits. Variation in β‐adrenoceptor genes is an intense focus of investigation because β‐adrenoceptors are: (1) ubiquitous in organ system distribution; (2) integral to a multitude of physiological processes; (3) well described in cardiovascular and metabolic disease; and (4) major pharmacological treatment targets. Furthermore, knowledge of functional gene variants in these receptors predates the description of the human genome. This review highlights the influence of common gene variation in the three β‐adrenoceptor subtypes on intermediate physiological phenotype predictive of cardiovascular disease and obesity. Although further information is needed to replicate this information across populations, this review condenses and summarizes growing trends in specific pleiotropic effects of β‐adrenoceptor polymorphisms and suggests which variants may be predictive of distant phenotype.

Levetiracetam Pharmacokinetics in a Patient Receiving Continuous Venovenous Hemofiltration and Venoarterial Extracorporeal Membrane Oxygenation

Levetiracetam is a first‐line therapy for seizures in critically ill patients because of its clinical efficacy, minimal drug interactions, and wide therapeutic window. The primary mechanism of levetiracetam clearance is renal, and the drug has a low molecular weight. It is hydrophilic and exhibits minimal protein binding. Thus it is expected that levetiracetam will be removed by continuous venovenous hemofiltration (CVVH), with limited clearance by venoarterial extracorporeal membrane oxygenation (ECMO). We describe the case of a 67‐year‐old man who was admitted to the cardiovascular surgery intensive care unit after cardiac arrest and initiation of venoarterial ECMO. His course was complicated by multiorgan dysfunction including acute renal failure requiring CVVH. On hospital day 6, intravenous levetiracetam, at a loading dose of 2000 mg followed by a maintenance dose of 1000 mg every 12 hours, was initiated for new‐onset seizures. The volume of distribution was 0.65 L/kg, and clearance was measured with peak (ranging from 26.5–39.8 μg/ml) and trough (ranging from 13.9–18.2 μg/ml) concentrations. Elimination half‐life ranged from 8.7–10.1 hours. Renal dysfunction reduces levetiracetam clearance, and dosage reductions are recommended to prevent accumulation. Current CVVH dosing recommendations are based on predicted removal without clinical data. The volume of distribution and clearance in this case were similar to those of a normal healthy patient. Based on these results, we recommend considering an initial levetiracetam dose of 1000 mg every 12 hours for patients receiving CVVH, with dosage adjustments based on therapeutic drug monitoring.

AngioVac Removal of a Saddle Pulmonary Embolus Using TEE Guidance and Venoarterial ECMO Support

VENOUS THROMBOEMBOLIC disease is a significant cause of morbidity and mortality, and in patients with hemodynamic instability, intervention with thrombolysis or embolectomy is indicated. In patients whose condition is otherwise stable, the use of thrombolysis or embolectomy has been advocated in the presence of right ventricular strain, patent foramen ovale, extensive clot burden, free-floating right heart thrombus, or severe hypoxemia. When the risk of bleeding precludes the use of thrombolytics, either surgical or catheter-based embolectomy prevails as the most acceptable treatment option. The Vortex AngioVac system (Vortex Medical, Inc; Marlborough, MA) is a catheter-based embolectomy system approved by the U.S. Food and Drug Administration for the percutaneous retrieval of unwanted intravascular material. The AngioVac cannula is paired with a thrombus filter, a centrifugal pump head, and a reinfusion cannula that returns blood to the patient’s venous circulation. The authors present a case in which the AngioVac system was used to retrieve a saddle pulmonary embolus under transesophageal echocardiographic (TEE) guidance. Because of concern for cardiorespiratory collapse during the procedure, the reinfusion cannula was modified with the addition of a venoarterial extracorporeal membrane oxygenation (ECMO) circuit.

Analgesia after Cesarean delivery: a retrospective comparison of intrathecal hydromorphone and morphine ☆

STUDY OBJECTIVE To compare analgesia and opioid-related side effects of intrathecal morphine and intrathecal hydromorphone after elective Cesarean delivery. DESIGN Retrospective, comparative study. SETTING Labor and delivery unit of an academic hospital. PATIENTS 114 parturients age ≥ 18 years, presenting for elective Cesarean delivery. INTERVENTIONS Patients who received 0.04 mg intrathecal hydromorphone were compared to a random sample of patients who received 0.1 mg intrathecal morphine for postoperative analgesia. MEASUREMENTS The primary outcome was the presence of any opioid-related complication (pruritus, nausea or vomiting, respiratory depression) requiring treatment within 24 hours of intrathecal opioid administration. Secondary outcomes included total opioid consumption (in oral morphine equivalents) within 24 hours of intrathecal opioid administration and verbal pain score (0 = none, 10 = worst) at 4, 8, 12, 18, and 24 hours after intrathecal opioid administration. MAIN RESULTS 38 patients who received intrathecal hydromorphone 0.04 mg were compared with 76 patients given 0.1 mg of intrathecal morphine for elective Cesarean delivery. No significant differences in demographics were noted between groups. There were no statistically significant differences between the intrathecal hydromorphone and intrathecal morphine groups in overall frequency of opioid-related complications (50% vs. 34.2%; P = 0.11), 24-hour opioid consumption (33 mg oral morphine equivalent [OME] vs. 8 mg OME; P = 0.27), or pain scores at any time point up to 24 hours. CONCLUSIONS Overall, analgesia and incidence of opioid-related side effects after 0.04 mg of intrathecal hydromorphone did not differ statistically from 0.1 mg of intrathecal morphine.

Myoclonus in patient on fluoxetine after receiving fentanyl and low-dose methylene blue during sentinel lymph node biopsy.

Serotonin released in the nerve synapses is cleared through reuptake into presynaptic neurons and metabolism with monoamine oxidase (MAO). Therapy with selective serotonin reuptake inhibitors (SSRIs) or MAO inhibitors increases serotonin concentration in the synaptic cleft and may result in serotonin syndrome (SS). Our patient undergoing sentinel lymph node biopsy was on fluoxetine (SSRI) and intraoperatively developed SS after receiving fentanyl (200 μg) and methylene blue (MAO inhibitor), 7 mg subcutaneously into the scalp. Initial presentation was several episodes of generalized muscle activity, which was later diagnosed as lower extremity myoclonus consistent with SS. Upon awakening, the patient showed no evidence of encephalopathy, and the clonus was less intense. The patient was discharge home the next day. Our case suggests the possibility that even a small dose of methylene blue, when administered simultaneously with other serotoninergic medications, may be associated with serotonin toxicity.

Urgent Ultrasound-Guided Bilateral Stellate Ganglion Blocks in a Patient With Medically Refractory Ventricular Arrhythmias.

Objectives:To describe the successful treatment of medically refractory ventricular arrhythmias in the ICU with ultrasound-guided bilateral stellate ganglion blocks. Data Sources:The data were gathered from the medical record. Study Selection:This case was selected as it describes the use of ultrasound in the successful termination of a recurrent, malignant arrhythmia, rather than fluoroscopy, to perform bilateral stellate ganglion blocks at the patient’s bedside in the ICU. Data Extraction:The data were extracted from the medical record. Data Synthesis:The data were synthesized from the patient’s medical record. Conclusions:Performance of stellate ganglion blocks at the bedside in the ICU is feasible for patients who are suffering from refractory ventricular arrhythmias. This potentially life-saving block can be performed using ultrasound guidance, sparing the patient transport to a fluoroscopy suite.

The incidence of vasoplegia in adult patients with right-sided congenital heart defects undergoing cardiac surgery and the correlation with serum vasopressin concentrations.

BACKGROUND In adults with right-sided congenital heart disease, vasoplegia during and after cardiopulmonary bypass appears to be a frequent complication. The incidence of vasoplegia in the general adult and pediatric cardiac surgical population has been investigated, but the incidence in adult patients with right-sided congenital heart disease is unknown. Perioperative vasopressin levels during cardiac surgery have been studied in other cardiac surgical patients, but are not known in adults with right-sided congenital heart disease. The purpose of this study was to investigate the incidence of vasoplegia in adult patients undergoing right-sided cardiac surgical procedures requiring cardiopulmonary bypass and to determine the vasopressin response to cardiac surgery in this population. METHODS Twenty patients were enrolled and demographic, hemodynamic, cardiopulmonary bypass, and use of vasoactive medication data were collected. In addition, perioperative serum vasopressin levels were measured. Sixty adult patients undergoing left-sided cardiac surgery served as controls. RESULTS The incidence of vasoplegia in the control patients was 10% and the incidence in the adult patients with right-sided congenital heart disease was 20%. Vasopressin levels were low at baseline (0.5 ± 0.5 pg/mL), increased slightly after induction of anesthesia (0.6 ± 0.6 pg/mL), increased after initiation of cardiopulmonary bypass (99.7 ± 168.2 pg/mL), and decreased after surgery (31.3 ± 43.6 pg/mL). CONCLUSIONS This study showed that the incidence of vasoplegia (20%) in patients with right-sided congenital heart disease undergoing cardiac surgery was double that of a population of patients undergoing aortic valve surgery (10%). Serum vasopressin concentration was not associated with vasoplegia in this population of congenital cardiac surgical patients.

Left Main Coronary Artery Compression following Melody Pulmonary Valve Implantation: Use of Impella Support as Rescue Therapy and Perioperative Challenges with ECMO

The purpose of this case is to describe the complex perioperative management of a 30-year-old woman with congenital heart disease and multiple resternotomies presenting with pulmonary homograft dysfunction and evaluation for percutaneous pulmonary valve replacement. Transvenous, transcatheter Melody valve placement caused left main coronary artery occlusion and cardiogenic shock. An Impella ventricular assist device (VAD) provided rescue therapy during operating room transport for valve removal and pulmonary homograft replacement. ECMO support was required following surgery. Several days later during an attempted ECMO wean, her hemodynamics deteriorated abruptly. Transesophageal and epicardial echocardiography identified pulmonary graft obstruction, requiring homograft revision due to large thrombosis. This case illustrates a role for Impella VAD as bridge to definitive procedure after left coronary occlusion and describes management of complex perioperative ECMO support challenges.

Severe Acute Cardiopulmonary Failure Related to Gadobutrol Magnetic Resonance Imaging Contrast Reaction: Successful Resuscitation with Extracorporeal Membrane Oxygenation

Nonanaphylactic noncardiogenic pulmonary edema leading to cardiorespiratory arrest related to the magnetic resonance imaging contrast agent gadobutrol has rarely been reported in the literature. Rarer is the association of hypokalemia with acidosis. We report 2 patients who had severe pulmonary edema associated with the use of gadobutrol contrast in the absence of other inciting agents or events. These cases were unique not only for their rare and severe presentations but also because they exemplified the increasing role of extracorporeal membrane oxygenation in resuscitation. Emergency extracorporeal membrane oxygenation resuscitation can be rapidly initiated and successful in the setting of a well-organized workflow, and it is a viable alternative and helps improve patient outcome in cases refractory to conventional resuscitative measures.

High-dose hydroxocobalamin for vasoplegic syndrome causing false blood leak alarm

Abstract Blood leak alarms are important safety features in a hemodialysis machine to protect patients from loss of blood through a rupture in the dialyzer membrane (true alarms). A false blood leak alarm can be triggered by air bubbles or detector malfunction (such as deposits of grease or scale). Hydroxocobalamin is an injectable form of vitamin B12 approved by the US Food and Drug Administration for the treatment of confirmed or suspected cyanide toxicity. Due to observations of an increase in arterial pressure after high-dose hydroxocobalamin infusion for the treatment of acute cyanide poisoning, it has recently been reported as an off-label rescue treatment for post–cardiopulmonary bypass vasoplegic syndrome. We report an 83-year-old man who received hydroxocobalamin following cardiac surgery for treatment of vasoplegic syndrome. The patient developed severe acute kidney injury with volume overload. Hydroxocobalamin interference with the blood leak detector compromised his dialysis treatment. We describe the use of continuous renal replacement therapy to overcome the hydroxocobalamin-related interference with hemodialysis. As the utility of hydroxocobalamin potentially expands, physicians must be aware of its inadvertent effect on renal replacement therapy.