Alix Zuleta-Alarcon

Perioperative Use of Clevidipine: A Systematic Review and Meta-Analysis

Background Clevidipine is an ultrashort-acting drug for rapid reduction of blood pressure by selectively acting on the L-type Ca2+ channels on arteriolar smooth muscle. The drug’s ultrashort action in reducing the blood pressure is due to its rapid hydrolysis by blood and extravascular tissue esterases, which does not depend on hepato-renal metabolism and excretion. An analysis of the perioperative management of blood pressure should be considered to compare with other intravenous antihypertensive agents. Methods Analyses of the available evidence in randomized clinical trials following the PRISMA methodology as well as clinical significance according to the GRADE system were conducted. Placebo versus other antihypertensive drugs studies were included. Statistical assessments were done using the X2 and I2 tests. Results Clevidipine was more effective in maintaining the blood pressure within pre-specified ranges compared with other antihypertensive drugs (MD, -17.87 CI 95%: -29.02 to -6.72; p = 0.02). The use of Clevidipine versus placebo and rescue antihypertensive intravenous drug showed a clear reduction in rates of treatment failure (RR 0.10; IC 95%; 0.05–0.18; p <0.0001). There was no difference in the incidence of adverse events compared with placebo (RR 1.47; 95% CI 0.89 to 2.43, p = 0.14) and with other antihypertensive drugs (RR 0.78, 95% CI 0.45 to 1.35; p = 0.37). In addition, there was no difference in the incidence of atrial fibrillation (AF) between clevidipine and control groups (RR 1.09, IC del 95%: 0.65 a 1.83; p = 0.73). Conclusions Clevidipine is an ultrafast-acting drug that is highly effective for management of perioperative arterial hypertension. It is devoid of adverse effects associated with the use of other IV antihypertensives. Its favorable pharmacodynamic and pharmacokinetic properties make clevidipine the drug of choice for the management of acute perioperative hypertension. It is important to emphasize the need for further studies with a larger number of patients to confirm these findings and increase the degree of evidence.

Mechanosensory Signaling in Enterochromaffin Cells and 5-HT Release: Potential Implications for Gut Inflammation

Enterochromaffin (EC) cells synthesize 95% of the body 5-HT and release 5-HT in response to mechanical or chemical stimulation. EC cell 5-HT has physiological effects on gut motility, secretion and visceral sensation. Abnormal regulation of 5-HT occurs in gastrointestinal disorders and Inflammatory Bowel Diseases (IBD) where 5-HT may represent a key player in the pathogenesis of intestinal inflammation. The focus of this review is on mechanism(s) involved in EC cell “mechanosensation” and critical gaps in our knowledge for future research. Much of our knowledge and concepts are from a human BON cell model of EC, although more recent work has included other cell lines, native EC cells from mouse and human and intact mucosa. EC cells are “mechanosensors” that respond to physical forces generated during peristaltic activity by translating the mechanical stimulus (MS) into an intracellular biochemical response leading to 5-HT and ATP release. The emerging picture of mechanosensation includes Piezo 2 channels, caveolin-rich microdomains, and tight regulation of 5-HT release by purines. The “purinergic hypothesis” is that MS releases purines to act in an autocrine/paracrine manner to activate excitatory (P2Y1, P2Y4, P2Y6, and A2A/A2B) or inhibitory (P2Y12, A1, and A3) receptors to regulate 5-HT release. MS activates a P2Y1/Gαq/PLC/IP3-IP3R/SERCA Ca2+signaling pathway, an A2A/A2B–Gs/AC/cAMP-PKA signaling pathway, an ATP-gated P2X3 channel, and an inhibitory P2Y12-Gi/o/AC-cAMP pathway. In human IBD, P2X3 is down regulated and A2B is up regulated in EC cells, but the pathophysiological consequences of abnormal mechanosensory or purinergic 5-HT signaling remain unknown. EC cell mechanosensation remains poorly understood.

Effect of goal-directed haemodynamic therapy on postoperative complications in low–moderate risk surgical patients: a multicentre randomised controlled trial (FEDORA trial)

Background: The aim of this study was to evaluate postoperative complications in patients having major elective surgery using oesophageal Doppler monitor‐guided goal‐directed haemodynamic therapy (GDHT), in which administration of fluids, inotropes, and vasopressors was guided by stroke volume, mean arterial pressure, and cardiac index. Methods: The FEDORA trial was a prospective, multicentre, randomised, parallel‐group, controlled patient‐ and observer‐blind trial conducted in adults scheduled for major elective surgery. Randomization and allocation were carried out by a central computer system. In the control group, intraoperative fluids were given based on traditional principles. In the GDHT group, the intraoperative goals were to maintain a maximal stroke volume, with mean arterial pressure >70 mm Hg, and cardiac index ≥2.5 litres min−1 m−2. The primary outcome was percentage of patients with moderate or severe postoperative complications during the first 180 days after surgery. Results: In total, 450 patients were randomized to the GDHT group (n=224) or control group (n=226). Data from 420 subjects were analysed. There were significantly fewer with complications in the GDHT group (8.6% vs 16.6%, P=0.018). There were also fewer complications (acute kidney disease, pulmonary oedema, respiratory distress syndrome, wound infections, etc.), and length of hospital stay was shorter in the GDHT group. There was no significant difference in mortality between groups. Conclusions: Oesophageal Doppler monitor‐guided GDHT reduced postoperative complications and hospital length of stay in low–moderate risk patients undergoing intermediate risk surgery, with no difference in mortality at 180 days. Clinical trial registration: ISRCTN93543537.

Perioperative Cognitive Protection—Cognitive Exercise and Cognitive Reserve (The Neurobics Trial): A Single-blind Randomized Trial

PURPOSE The Neurobics Trial is a single-blind, parallel-group, randomized, controlled trial. The main study objective is to compare effectiveness of preoperative cognitive exercise versus no intervention for lowering the incidence of postoperative delirium. Enrollment began March 2015 and is ongoing. METHODS Eligible participants include patients older than 60 years of age scheduled for nonemergent, noncardiac, nonneurological surgery at our institution. Patients provide consent and are screened at our Outpatient Preoperative Assessment Clinic to rule out preexisting cognitive dysfunction, significant mental health disorders, and history of surgery requiring general anesthesia in the preceding 6 months. Participants meeting criteria are randomized to complete 1 hour daily of electronic tablet-based cognitive exercise for 10 days before surgery or no preoperative intervention. Compliance with the effective dose of 10 total hours of preoperative exercise is verified on return of the patient for surgery with time logs created by the software application and by patient self-reporting. After surgery, patients are evaluated for delirium in the postanesthesia recovery area, and then twice daily for the remainder of their hospitalization. Additionally, postoperative quality of recovery is assessed daily, along with pain scores and opiate use. More comprehensive cognitive assessments are completed just before discharge for baseline comparison, and quality of recovery is assessed via telephone interview 7, 30, and 90 days post-surgery. The primary outcome is the incidence of delirium during the postoperative hospitalization period. Randomization is computer generated, with allocation concealment in opaque envelopes. All postoperative assessments are completed by blinded study personnel. FINDINGS The study is actively recruiting with 19 patients having provided consent to date, and a total of 264 patients is required for study completion; therefore, no data analysis is currently under way (www.clinicaltrials.gov; NCT02230605). IMPLICATIONS To our knowledge, the Neurobics Trial is the first randomized, controlled study to investigate the effectiveness of a significant preoperative cognitive exercise regimen for the prevention of delirium after noncardiac, nonneurological surgery in elderly patients.

UTP – Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human Enterochromaffin Cells

Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to trigger or modulate gut neural reflexes and transmit information about visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms modulating Ca2+-dependent 5-HT release are not understood. Previous studies indicated that purinergic signaling via ATP and ADP is an important mechanism in modulation of 5-HT release. However, EC cells also respond to UTP and UDP suggesting uridine triphosphate receptor and signaling pathways are involved as well. We tested the hypothesis that UTP is a regulator of 5-HT release in human EC cells. Methods: UTP signaling mechanisms were studied in BON cells, a human EC model, using Fluo-4/Ca2+imaging, patch-clamp, pharmacological analysis, immunohistochemistry, western blots and qPCR. 5-HT release was monitored in BON or EC isolated from human gut surgical specimens (hEC). Results: UTP, UTPγS, UDP or ATP induced Ca2+oscillations in BON. UTP evoked a biphasic concentration-dependent Ca2+response. Cells responded in the order of UTP, ATP > UTPγS > UDP >> MRS2768, BzATP, α,β-MeATP > MRS2365, MRS2690, and NF546. Different proportions of cells activated by UTP and ATP also responded to UTPγS (P2Y4, 50% cells), UDP (P2Y6, 30%), UTPγS and UDP (14%) or MRS2768 (<3%). UTP Ca2+responses were blocked with inhibitors of PLC, IP3R, SERCA Ca2+pump, La3+sensitive Ca2+channels or chelation of intracellular free Ca2+ by BAPTA/AM. Inhibitors of L-type, TRPC, ryanodine-Ca2+pools, PI3-Kinase, PKC or SRC-Kinase had no effect. UTP stimulated voltage-sensitive Ca2+currents (ICa), Vm-depolarization and inhibited IK (not IA) currents. An IKv7.2/7.3 K+ channel blocker XE-991 mimicked UTP-induced Vm-depolarization and blocked UTP-responses. XE-991 blocked IK and UTP caused further reduction. La3+ or PLC inhibitors blocked UTP depolarization; PKC inhibitors, thapsigargin or zero Ca2+buffer did not. UTP stimulated 5-HT release in hEC expressing TPH1, 5-HT, P2Y4/P2Y6R. Zero-Ca2+buffer augmented Ca2+responses and 5-HT release. Conclusion: UTP activates a predominant P2Y4R pathway to trigger Ca2+oscillations via internal Ca2+mobilization through a PLC/IP3/IP3R/SERCA Ca2+signaling pathway to stimulate 5-HT release; Ca2+influx is inhibitory. UTP-induced Vm-depolarization depends on PLC signaling and an unidentified K channel (which appears independent of Ca2+oscillations or Ica/VOCC). UTP-gated signaling pathways triggered by activation of P2Y4R stimulate 5-HT release.

Non-opioid anesthetic drug abuse among anesthesia care providers: a narrative review.

PurposeThe objective of this narrative review is to provide an overview of the problem of non-opioid anesthetic drug abuse among anesthesia care providers (ACPs) and to describe current approaches to screening, therapy, and rehabilitation of ACPs suffering from non-opioid anesthetic drug abuse.SourceWe first performed a search of all literature available on PubMed prior to April 11, 2016. The search was limited to articles published in Spanish and English, and the following key words were used: anesthesiology, anesthesia personnel, AND substance-related disorders. We also searched Ovid MEDLINE® databases from 1946-April 11, 2016 using the following search terms: anesthesiology OR anesthesia, OR nurse anesthetist OR anesthesia care provider OR perioperative nursing AND substance-related disorders.Principal findingsDespite an increased awareness of drug abuse among ACPs and improvements in preventive measures, the problem of non-opioid anesthetic drug abuse remains significant. While opioids are the most commonly abused anesthesia medications among ACPs, the abuse of non-opioid anesthetics is a significant cause of morbidity, mortality, and professional demise.ConclusionEarly detection, effective therapy, and long-term follow-up help ACPs cope more effectively with the problem and, when possible, resume their professional activities. There is insufficient evidence to determine the ability of ACPs to return safely to anesthesia practice after rehabilitation, though awareness of the issue and ongoing treatment are necessary to minimize patient risk from potentially related clinical errors.RésuméObjectifL’objectif de ce compte rendu est de présenter une vue d’ensemble du problème d’abus de médicaments anesthésiques non opioïdes parmi le personnel d’anesthésie et de décrire les approches de dépistage, de traitement et de réhabilitation actuellement à la disposition du personnel d’anesthésie souffrant d’un abus de médicaments anesthésiques non opioïdes.SourceNous avons commencé par réaliser une recherche de toute la littérature disponible sur PubMed avant le 11 avril 2016. La recherche se limitait aux articles publiés en espagnol et en anglais, et les mots clés suivants ont été utilisés: anesthésiologie, personnel d’anesthésie, ET troubles liés à l’abus de substance. Nous avons également effectué une recherche dans les bases de données Ovid MEDLINE® entre 1946 et le 11 avril 2016 à l’aide des termes de recherche suivants: anesthésiologie OU anesthésie, OU infirmière anesthésiste OU personnel d’anesthésie OU soins infirmiers périopératoires ET troubles liés à l’abus de substances (soit: ‘anesthesiology’ ou ‘anesthesia’, ou ‘nurse anesthetist’ ou ‘anesthesia care provider’ ou ‘perioperative nursing’ et ‘substance-related disorders’).Constatations principalesMalgré une meilleure prise de conscience de l’abus de médicaments parmi le personnel d’anesthésie et les progrès en matière de mesures préventives, le problème qu’est l’abus de médicaments anesthésiques non opioïdes demeure considérable. Bien que les opioïdes soit les médicaments les plus fréquemment rencontrés dans les problèmes d’abus de médicaments anesthésiques chez le personnel d’anesthésie, l’abus de médicaments anesthésiques non opioïdes constitue néanmoins une importante cause de morbidité, de mortalité et de terminaison de carrière.ConclusionLe dépistage précoce, un traitement efficace et un suivi à long terme peuvent aider le personnel d’anesthésie à mieux gérer le problème et, lorsque cela est possible, reprendre leurs activités professionnelles. Les données probantes ne sont pas suffisantes pour attester que le personnel d’anesthésie peut revenir en toute sécurité à la pratique de l’anesthésie après réhabilitation, mais la prise de conscience du problème et un traitement continu sont nécessaires afin de minimiser le risque encouru par les patients d’erreurs cliniques potentiellement liées à ces abus.

Elevated Transaortic Valvular Gradients After Combined Aortic Valve and Mitral Valve Replacement An Intraoperative Dilemma

High transaortic valvular gradients, after combined aortic valve and mitral valve replacement, require prompt intraoperative diagnosis and appropriate management. The presence of high transaortic valvular gradients after cardiopulmonary bypass, in this setting, can be secondary to the following conditions: prosthesis dysfunction, left ventricular outflow tract obstruction, supravalvular obstruction, prosthesis–patient mismatch, hyperkinetic left ventricle from administration of inotropes, left ventricular intracavitary gradients, pressure recovery phenomenon, and increased transvalvular blood flow resulting from hyperdynamic circulation or anemia. Transesophageal echocardiography is an extremely useful tool for timely diagnosis and treatment of this complication. We describe a case of a critically ill patient with endocarditis and acute lung injury, who presented for combined aortic valve and mitral valve replacement. Transesophageal echocardiographic assessment, post–cardiopulmonary bypass, revealed high transaortic valvular gradients due to encroachment of the mitral prosthesis strut on the left ventricular outflow tract, which was compounded by a small, hypertrophied, and hyperkinetic left ventricle. Discontinuation of inotropic support, administration of fluids, phenylephrine, and esmolol led to resolution of the high gradients and prevented further surgery.

Mitral Valve Annuloplasty Ring Dehiscence Diagnosed Intraoperative With Real-Time 3D Transesophageal Echocardiogram

Mitral annular calcification (MAC) is often a result of the accumulation of lipids around the annulus, which can lead to degeneration and calcification of the valve. Multiple risk factors have been associated with the progression of MAC and life-threatening complications such as the early mitral valve annuloplasty dehiscence. Our case describes the different risk factors for annuloplasty dehiscence in a patient with severe MAC, as well as the importance of its early recognition intraoperatively with 3D transesophageal echocardiography.

Intraoperative Seizures: Anesthetic and Antiepileptic Drugs

BACKGROUND Epilepsy is a common condition with up to 1% prevalence in the general population. In the perioperative course of neurologic surgery patients, the use of prophylactic and therapeutic antiepileptic drugs is a common practice. Nonetheless, there is limited evidence supporting the use of prophylactic antiepileptics to prevent perioperative seizures and there are no guidelines for which anesthetic technique is preferred. OBJECTIVE To discuss the seizurogenic potential of anesthetic drugs and to discuss intraoperative seizures in neurosurgical patients. METHOD We performed a search of the literature available in PubMed and Ovid MEDLINE. We also included articles identified in the review of the references of these articles. RESULTS The incidence of seizures is heterogenic among neurosurgical patients. Seizure prophylaxis is widely administered despite limited available evidence of its effectiveness. In epileptic patients, the recommendation is to continue antiepileptic drugs in the perioperative setting. In these patients, anesthesiologists may also limit the use of medications that alter the seizure threshold and avoid medications that pose significant pharmacological interaction with antiepileptic drugs. CONCLUSION In conclusion, a knowledgeable multidisciplinary perioperative team is essential to avoid, identify and treat intraoperative seizures competently. In patients with a history of epilepsy it is recommended to continue antiepileptic therapy. Therefore, clinical judgment should guide the decision of administering seizure prophylaxis in neurosurgery patients according to an individual assessment of potential risk for seizures. Furthermore, there is a need for randomized controlled trials that support new protocols and/or guidelines for anesthetic and perioperative regimens to prevent and treat intraoperative seizures.

Transesophageal Echocardiographic Diagnosis of Severe Functional Tricuspid Stenosis During Infected Implantable Cardioverter-Defibrillator Lead Extraction

raphy (TEE) is a safe and highly sensitive technique in the diagnosis of CDIE. Coupling TEE with transthoracic echocardiography (TTE) can further provide clinically useful information in determining whether patients require surgical or transvenous lead extraction. The utilization of TEE in high-risk patients provides valuable and real-time information for hemodynamic status, cardiac anatomy, and cardiac function. There are many complications related to implantable cardioverter-defibrillator (ICD) lead extraction, including, but not limited to, septic pulmonary and systemic emboli, tricuspid valvular apparatus injury, right ventricular (RV) dysfunction secondary to myocardial distortion or inversion, cardiac perforation, and cardiac tamponade. 3,4 The authors present a case report highlighting the value of TEE for early recognition and management of hemodynamic complications associated with transvenous lead extraction.