Publications by authors named "Srikanth Sridhar"

22 Publications

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Adult liver transplant anesthesiology practice patterns and resource utilization in the United States: Survey results from the society for the advancement of transplant anesthesia.

Clin Transplant 2021 Oct 12:e14504. Epub 2021 Oct 12.

Department of Anesthesiology, University of Colorado, Aurora, CO.

Introduction: Liver transplant anesthesiology is an evolving and expanding subspecialty, and programs have, in the past, exhibited significant variations of practice at transplant centers across the United States. In order to explore current practice patterns, the Quality & Standards Committee from the Society for the Advancement of Transplant Anesthesia (SATA) undertook a survey of liver transplant anesthesiology program directors.

Methods: Program directors were invited to participate in an online questionnaire. A total of 110 program directors were identified from the 2018 Scientific Registry of Transplant Recipients (SRTR) database. Replies were received from 65 programs (response rate of 59%).

Results: Our results indicate an increase in transplant anesthesia fellowship training and advanced training in transesophageal echocardiography (TEE). We also find that the use of intraoperative TEE and viscoelastic testing is more common. However, there has been a reduction in the use of veno-venous bypass, routine placement of pulmonary artery catheters and the intraoperative use of anti-fibrinolytics when compared to prior surveys.

Conclusion: The results show considerable heterogeneity in practice patterns across the country that continues to evolve. However, there appears to be a movement towards the adoption of specific structural and clinical practices. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/ctr.14504DOI Listing
October 2021

Whole Blood in Modern Anesthesia Practice.

Adv Anesth 2020 12 5;38:115-129. Epub 2020 Oct 5.

Department of Anesthesiology, McGovern Medical School at UTHealth, 6431 Fannin Street, MSB 5.020, Houston, TX 77030, USA. Electronic address:

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http://dx.doi.org/10.1016/j.aan.2020.08.001DOI Listing
December 2020

(Carbonyl)oxyalkyl linker-based amino acid prodrugs of the HIV-1 protease inhibitor atazanavir that enhance oral bioavailability and plasma trough concentration.

Eur J Med Chem 2020 Dec 21;207:112749. Epub 2020 Aug 21.

Department of Small Molecule Drug Discovery, Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ, 08543-4000, United States.

We describe the design, synthesis and pharmacokinetic (PK) evaluation of a series of amino acid-based prodrugs of the HIV-1 protease inhibitor atazanavir (1) derivatized on the pharmacophoric secondary alcohol using a (carbonyl)oxyalkyl linker. Prodrugs of 1 incorporating simple (carbonyl)oxyalkyl-based linkers and a primary amine in the promoiety were found to exhibit low chemical stability. However, chemical stability was improved by modifying the primary amine moiety to a tertiary amine, resulting in a 2-fold enhancement of exposure in rats following oral dosing compared to dosing of the parent drug 1. Further refinement of the linker resulted in the discovery of 22 as a prodrug that delivered the parent 1 to rat plasma with a 5-fold higher AUC and 67-fold higher C when compared to oral administration of the parent drug. The PK profile of 22 indicated that plasma levels of this prodrug were higher than that of the parent, providing a more sustained release of 1 in vivo.
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http://dx.doi.org/10.1016/j.ejmech.2020.112749DOI Listing
December 2020

Service Requirements of Liver Transplant Anesthesia Teams: Society for the Advancement of Transplant Anesthesia Recommendations.

Liver Transpl 2020 04 10;26(4):582-590. Epub 2020 Mar 10.

Department of Anesthesiology, University of Colorado, Aurora, CO.

There are disparities in liver transplant anesthesia team (LTAT) care across the United States. However, no policies address essential resources for liver transplant anesthesia services similar to other specialists. In response, the Society for the Advancement of Transplant Anesthesia appointed a task force to develop national recommendations. The Conditions of Transplant Center Participation were adapted to anesthesia team care and used to develop Delphi statements. A Delphi panel was put together by enlisting 21 experts from the fields of liver transplant anesthesiology and surgery, hepatology, critical care, and transplant nursing. Each panelist rated their agreement with and the importance of 17 statements. Strong support for the necessity and importance of 13 final items were as follows: resources, including preprocedure anesthesia assessment, advanced monitoring, immediate availability of consultants, and the presence of a documented expert in liver transplant anesthesia credentialed at the site of practice; call coverage, including schedules to assure uninterrupted coverage and methods to communicate availability; and characteristics of the team, including membership criteria, credentials at the site of practice, and identification of who supervises patient care. Unstructured comments identified competing time obligations for anesthesia and transplant services as the principle reason that the remaining recommendations to attend integrative patient selection and quality review committees were reduced to a suggestion rather than being a requirement. This has important consequences because deficits in team integration cause higher failure rates in service quality, timeliness, and efficiency. Solutions are needed that remove the time-related financial constraints of competing service requirements for anesthesiologists. In conclusion, using a modified Delphi technique, 13 recommendations for the structure of LTATs were agreed upon by a multidisciplinary group of experts.
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http://dx.doi.org/10.1002/lt.25711DOI Listing
April 2020

Comparison of temporal artery temperature and bladder temperature in the postanesthesia care unit.

Proc (Bayl Univ Med Cent) 2019 Oct 15;32(4):502-504. Epub 2019 Jul 15.

Department of Anesthesiology, University of Texas McGovern Medical SchoolHoustonTexas.

To verify that temporal artery (TA) temperature measured in the postanesthesia care unit (PACU) in noncardiac surgical patients is a valid reflection of core temperature, a prospective, observational, institutional review board-approved study was conducted in a large, academic tertiary care hospital. The study developed from an initial quality improvement project. A total of 276 patients who had an indwelling bladder catheter as standard of care were enrolled when a research student was available over a 6-month period in 2015. Infrared TA temperature was measured (average of three readings) simultaneously with bladder temperature on PACU arrival. Mean temperature in the bladder and TA groups was >36°C with a clinically negligible difference (0.125°C; 90% confidence interval, 0.059-0.192). Agreement between bladder and TA temperatures, as well as between bladder and last operating room temperatures, was >95% by Bland-Altman analysis. A properly performed TA temperature measure on PACU arrival is an acceptable representation of core temperature for purposes of quality assessment, patient comfort, and regulatory requirements.
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http://dx.doi.org/10.1080/08998280.2019.1624097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6793965PMC
October 2019

Design, Synthesis, and Pharmacokinetic Evaluation of Phosphate and Amino Acid Ester Prodrugs for Improving the Oral Bioavailability of the HIV-1 Protease Inhibitor Atazanavir.

J Med Chem 2019 04 2;62(7):3553-3574. Epub 2019 Apr 2.

Phosphate and amino acid prodrugs of the HIV-1 protease inhibitor (PI) atazanavir (1) were prepared and evaluated to address solubility and absorption limitations. While the phosphate prodrug failed to release 1 in rats, the introduction of a methylene spacer facilitated prodrug activation, but parent exposure was lower than that following direct administration of 1. Val amino acid and Val-Val dipeptides imparted low plasma exposure of the parent, although the exposure of the prodrugs was high, reflecting good absorption. Screening of additional amino acids resulted in the identification of an l-Phe ester that offered an improved exposure of 1 and reduced levels of the circulating prodrug. Further molecular editing focusing on the linker design culminated in the discovery of the self-immolative l-Phe-Sar dipeptide derivative 74 that gave four-fold improved AUC and eight-fold higher C values of 1 compared with oral administration of the drug itself, demonstrating a successful prodrug approach to the oral delivery of 1.
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http://dx.doi.org/10.1021/acs.jmedchem.9b00002DOI Listing
April 2019

In Response.

Anesth Analg 2018 12;127(6):e106-e107

Department of Anesthesiology, UT Health McGovern Medical School, Houston, Texas, Gulf Coast Regional Blood Center, Houston, Texas Department of Surgery, UT Health McGovern Medical School, Houston, Texas.

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http://dx.doi.org/10.1213/ANE.0000000000003792DOI Listing
December 2018

Whole Blood for Resuscitation in Adult Civilian Trauma in 2017: A Narrative Review.

Anesth Analg 2018 07;127(1):157-162

Surgery, University of Texas Health McGovern Medical School, Houston, Texas.

After a hiatus of several decades, the concept of cold whole blood (WB) is being reintroduced into acute clinical trauma care in the United States. Initial implementation experience and data grew from military medical applications, followed by more recent development and data acquisition in civilian institutions. Anesthesiologists, especially those who work in acute trauma facilities, are likely to be presented with patients either receiving WB from the emergency department or may have WB as a therapeutic option in massive transfusion situations. In this focused review, we briefly discuss the historical concept of WB and describe the characteristics of WB, including storage, blood group compatibility, and theoretical hemolytic risks. We summarize relevant recent retrospective military and preliminary civilian efficacy as well as safety data related to WB transfusion, and describe our experience with the initial implementation of WB transfusion at our level 1 trauma hospital. Suggestions and collective published experience from other centers as well as ours may be useful to those investigating such a program. The role of WB as a significant therapeutic option in civilian trauma awaits further prospective validation.
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http://dx.doi.org/10.1213/ANE.0000000000003427DOI Listing
July 2018

Dramatic change in cerebral oximetry during liver transplantation.

Proc (Bayl Univ Med Cent) 2018 Apr 8;31(2):185-186. Epub 2018 Feb 8.

Department of Anesthesiology, University of Texas McGovern Medical School, Houston, Texas.

We report dramatic changes in bilateral cerebral tissue oxygenation in a patient undergoing an orthotopic liver transplant coincident with clamping and subsequent restoration of flow through the inferior vena cava. Although hemodynamic stability was maintained with low-dose vasopressor support, cardiac output was decreased, suggesting preload dependence of the measured cerebral oxygenation. Further investigation is warranted in patients with end-stage liver disease and interruption of venous return.
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http://dx.doi.org/10.1080/08998280.2017.1416238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914474PMC
April 2018

Coupling of an Acyl Migration Prodrug Strategy with Bio-activation To Improve Oral Delivery of the HIV-1 Protease Inhibitor Atazanavir.

J Med Chem 2018 05 25;61(9):4176-4188. Epub 2018 Apr 25.

HIV-1 protease inhibitors (PIs), which include atazanavir (ATV, 1), remain important medicines to treat HIV-1 infection. However, they are characterized by poor oral bioavailability and a need for boosting with a pharmacokinetic enhancer, which results in additional drug-drug interactions that are sometimes difficult to manage. We investigated a chemo-activated, acyl migration-based prodrug design approach to improve the pharmacokinetic profile of 1 but failed to obtain improved oral bioavailability over dosing the parent drug in rats. This strategy was refined by conjugating the amine with a promoiety designed to undergo bio-activation, as a means of modulating the subsequent chemo-activation. This culminated in a lead prodrug that (1) yielded substantially better oral drug delivery of 1 when compared to the parent itself, the simple acyl migration-based prodrug, and the corresponding simple l-Val prodrug, (2) acted as a depot which resulted in a sustained release of the parent drug in vivo, and (3) offered the benefit of mitigating the pH-dependent absorption associated with 1, thereby potentially reducing the risk of decreased bioavailability with concurrent use of stomach-acid-reducing drugs.
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http://dx.doi.org/10.1021/acs.jmedchem.8b00277DOI Listing
May 2018

The New Kidney Donor Allocation System and Implications for Anesthesiologists.

Semin Cardiothorac Vasc Anesth 2018 Jun 4;22(2):223-228. Epub 2017 Sep 4.

1 UTHealth McGovern Medical School, Houston, TX, USA.

Given potential disparity and limited allocation of deceased donor kidneys for transplantation, a new federal kidney allocation system was implemented in 2014. Donor organ function and estimated recipient survival in this system has implications for perioperative management of kidney transplant recipients. Early analysis suggests that many of the anticipated goals are being attained. For anesthesiologists, implications of increased dialysis duration and burdens of end-stage renal disease include increased cardiopulmonary disease, challenging fluid, hemodynamic management, and central vein access. With no recent evidence to guide anesthesia care within this new system, we describe the kidney allocation system, summarize initial data, and briefly review organ systems of interest to anesthesiologists. As additional invasive and echocardiographic monitoring may be indicated, one consideration may be development of a dedicated anesthesiology team experienced in management and monitoring of complex patients, in a similar manner as has been done for liver transplant recipients.
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http://dx.doi.org/10.1177/1089253217728128DOI Listing
June 2018

Targeting Hypoxia Signaling for Perioperative Organ Injury.

Anesth Analg 2018 01;126(1):308-321

From the Department of Anesthesiology, the University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas.

Perioperative organ injury has a significant impact on surgical outcomes and presents a leading cause of death in the United States. Recent research has pointed out an important role of hypoxia signaling in the protection from organ injury, including for example myocardial infarction, acute respiratory distress syndrome, acute kidney, or gut injury. Hypoxia induces the stabilization of hypoxia-inducible factors (HIFs), thereby leading to the induction of HIF target genes, which facilitates adaptive responses to low oxygen. In this review, we focus on current therapeutic strategies targeting hypoxia signaling in various organ injury models and emphasize potential clinical approaches to integrate these findings into the care of surgical patients. Conceptually, there are 2 options to target the HIF pathway for organ protection. First, drugs became recently available that promote the stabilization of HIFs, most prominently via inhibition of prolyl hydroxylase. These compounds are currently trialed in patients, for example, for anemia treatment or prevention of ischemia and reperfusion injury. Second, HIF target genes (such as adenosine receptors) could be activated directly. We hope that some of these approaches may lead to novel pharmacologic strategies to prevent or treat organ injury in surgical patients.
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http://dx.doi.org/10.1213/ANE.0000000000002288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735013PMC
January 2018

Resuscitative Endovascular Balloon Occlusion of the Aorta: Principles, Initial Clinical Experience, and Considerations for the Anesthesiologist.

Anesth Analg 2017 09;125(3):884-890

From the Departments of *Anesthesiology and †Surgery, University of Texas McGovern Medical School-Houston, Houston, Texas.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an endovascular technique that allows for temporary occlusion of the aorta in patients with severe, life-threatening, trauma-induced noncompressible hemorrhage arising below the diaphragm. REBOA utilizes a transfemoral balloon catheter inserted in a retrograde fashion into the aorta to provide inflow control and support blood pressure until definitive hemostasis can be achieved. Initial retrospective and registry clinical data in the trauma surgical literature demonstrate improvement in systolic blood pressure with balloon inflation and improved survival compared to open aortic cross-clamping via resuscitative thoracotomy. However, there are no significant reports of anesthetic implications and perioperative management in this challenging cohort. In this narrative, we review the principles, technique, and logistics of REBOA deployment, as well as initial clinical outcome data from our level-1 American College of Surgeons-verified trauma center. For anesthesiologists who may not yet be familiar with REBOA, we make several suggestions and recommendations for intraoperative management based on extrapolation from these initial surgical-based reports, opinions from a team with increasing experience, and translated experience from emergency aortic vascular surgical procedures. Further prospective data will be necessary to conclusively guide anesthetic management, especially as potential complications and implications for global organ function, including cerebral and renal, are recognized and described.
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http://dx.doi.org/10.1213/ANE.0000000000002150DOI Listing
September 2017

Unmasking the Role of Uptake Transporters for Digoxin Uptake Across the Barriers of the Central Nervous System in Rat.

J Cent Nerv Syst Dis 2017 15;9:1179573517693596. Epub 2017 Mar 15.

Pharmaceutical Candidate Optimization, Biocon Bristol-Myers Squibb Research & Development Center (BBRC), Bristol-Myers Squibb India Ltd, Bangalore, India.

The role of uptake transporter (organic anion-transporting polypeptide [Oatp]) in the disposition of a P-glycoprotein (P-gp) substrate (digoxin) at the barriers of central nervous system, namely, the blood-brain barrier (BBB), blood-spinal cord barrier (BSCB), and brain-cerebrospinal fluid barrier (BCSFB), was studied using rat as a preclinical species. In vivo chemical inhibition of P-gp and Oatp was achieved using elacridar and rifampicin, respectively. Our findings show that (1) digoxin had a low brain-to-plasma concentration ratio (B/P) (0.07) in rat; (2) in the presence of elacridar, the B/P of digoxin increased by about 12-fold; (3) rifampicin administration alone did not change the digoxin B/P significantly when compared with digoxin B/P alone; (4) rifampicin administration along with elacridar resulted only in 6-fold increase in the B/P of digoxin; (5) similar fold changes and trends were seen with the spinal cord-to-plasma concentration ratio of digoxin, indicating the similarity between BBB and the BSCB; and (6) unlike BBB and BSCB, the presence of rifampicin further increased the cerebrospinal fluid-to-plasma concentration ratio (CSF/P) for digoxin, suggesting a differential orientation of the uptake transporters at the BCSFB (CSF to blood) compared with the BBB (blood to brain). The observations for digoxin uptake, at least at the BBB and the BSCB, advocate the importance of uptake transporters (Oatps). However, the activity of such uptake transporters became evident only after inhibition of the efflux transporter (P-gp).
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http://dx.doi.org/10.1177/1179573517693596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392048PMC
March 2017

Single jugular vein cannulated rats may not be suitable for intravenous pharmacokinetic screening of high logP compounds.

Eur J Pharm Sci 2017 Mar 26;99:272-278. Epub 2016 Dec 26.

Pharmaceutical Candidate Optimization, Biocon Bristol-Myers Squibb R&D Centre (BBRC), Syngene International Ltd., Biocon Park, Plot 2 & 3, Bommasandra IV Phase, Bangalore 560099, India. Electronic address:

Rat is commonly used for pharmacokinetic screening during pharmaceutical lead optimization. To handle the large number of compounds, rats with a single jugular vein cannulation are commonly utilized for intravenous pharmacokinetic studies, where the same cannula is used both for dose administration and blood sampling. We demonstrate that the single cannula method is not suitable for all compounds, especially for high logP compounds. We propose an alternative dual cannulation technique in which two cannulas are placed in the same jugular vein, thus avoiding an additional surgery. Compounds were administered orally or via intravenous infusion to compare PK parameters, including bioavailability, using both procedures. For itraconazole and amiodarone, known to bind to the cannula, the measured plasma exposures were substantially higher in the single cannulated rats than those from dual cannulated rats. Area under the plasma concentration time curve differed by 79% and 74% for itraconazole and amiodarone, respectively. When compared to the single cannulation approach, clearance, volume of distribution and bioavailability determined by dual cannulation were 39%, 60% and 38% higher for itraconazole, and 46%, 34% and 42% higher for amiodarone, respectively. In contrast, all pharmacokinetic parameters were similar between single and dual-cannulated rats for the hydrophilic compound atenolol. Based on these results, we recommend the use of dual cannulated rats for intravenous pharmacokinetic studies when testing a series of hydrophobic compounds that may be prone to non-specific binding to the cannula. If single cannulated model is selected for pharmacokinetic screening, we recommend a bridging study with dual cannulated rats with representative compounds of a given chemical series.
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http://dx.doi.org/10.1016/j.ejps.2016.12.025DOI Listing
March 2017

All Work Hours Are Not Equal.

Anesthesiology 2016 06;124(6):1412-3

University of Texas Health Science Center, Houston, Texas (E.G.P.).

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http://dx.doi.org/10.1097/ALN.0000000000001092DOI Listing
June 2016

Is the "Triple Low" Association with Death Statistically Valid or Reflective of Clinical Practice?

Anesthesiology 2016 06;124(6):1410

University of Texas Medical School at Houston, Houston, Texas (E.G.P.).

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http://dx.doi.org/10.1097/ALN.0000000000001086DOI Listing
June 2016

Reliability of a faculty evaluated scoring system for anesthesiology resident applicants (Original Investigation).

J Clin Anesth 2016 Jun 15;31:131-6. Epub 2016 Apr 15.

Department of Anesthesiology, University of Texas Medical School at Houston, MSB 5.020, 6431 Fannin Street, Houston, TX, 77030. Electronic address:

Study Objective: To assess reliability and reproducibility of a recently instituted anesthesiology resident applicant interview scoring system at our own institution.

Design: Retrospective evaluation of 2 years of interview data with a newly implemented scoring system using randomly assigned interviewing faculty.

Setting: Interview scoring evaluations were completed as standard practice in a large academic anesthesiology department.

Subjects: All anesthesiology resident applicants interviewed over the 2013/14 and 2014/15 seasons by a stable cohort of faculty interviewers. Data collection blinded for both interviewers and interviewees.

Interventions: None for purposes of study - collation of blinded data already used as standard practice during interview process and analysis.

Measurements: None specific to study.

Main Results: Good inter-rater faculty reliability of interview scoring (day-of) and excellent inter-faculty reliability of application review (pre-interview).

Conclusions: Development of a department-specific interview scoring system including many elements beyond traditional standardized tests shows good-excellent reliability of faculty scoring of both the interview itself (including non-technical skills) and the application resume.
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http://dx.doi.org/10.1016/j.jclinane.2016.02.015DOI Listing
June 2016

Dangerous Regulations for a Level 1 Trauma Operating Room.

Anesth Analg 2016 Mar;122(3):921

Department of Anesthesiology, University of Texas Medical School at Houston, Houston, Texas,

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http://dx.doi.org/10.1213/ANE.0000000000001020DOI Listing
March 2016

Screening for sleep apnea in the perioperative setting: looking for the right compromise.

Minerva Anestesiol 2016 08 5;82(8):914-5. Epub 2016 Jan 5.

Department of Anesthesiology, University of Texas Medical School, Memorial Hermann Hospital, Texas Medical Center, Houston, TX, USA -

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August 2016

Assessing risk of obstructive sleep apnea by STOP-BANG questionnaire in an adult surgical population screened in the preoperative anesthesia clinic.

Minerva Anestesiol 2016 05 9;82(5):605-6. Epub 2015 Oct 9.

Departments of Anesthesiology and Internal Medicine, University of Texas Medical School at Houston, Memorial Hermann Hospital -, Texas Medical Center, Houston, TX, USA -

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May 2016

An evaluation of the rapid airway management positioner in obese patients undergoing gastric bypass or laparoscopic gastric banding surgery.

Obes Surg 2010 Oct 24;20(10):1436-41. Epub 2009 Jun 24.

Department of Anesthesiology, The University of Texas Medical School at Houston, 6431 Fannin, MSB 5.020, Houston, TX 77030, USA.

A new positioning device, the Rapid Airway Management Positioner (RAMP, Airpal Inc., Center Valley, PA) was evaluated to determine if there was an improvement in either mask ventilation, direct laryngoscopy, or both with the use of the RAMP in this patient population. Fifty-one morbidly obese patients (BMI > 35 kg/m(2)) undergoing elective bariatric surgery were enrolled. Ventilation and laryngoscopy was performed in the neutral and head-elevated laryngoscopy position (HELP). Direct laryngoscopy was performed noting the glottic view according to the Cormack-Lehane classification (Samsoon and Young, Anesthesiology 42:487, 1987). Mask ventilation was then recommenced. The HELP, or "ramped," position was achieved by inflating the RAMP, which was placed underneath the patient prior to entering the OR. Once proper HELP position was achieved, a second laryngoscopy was performed followed by endotracheal intubation. Two main outcomes were noted in the neutral and HELP positions: (1) laryngoscopic view and (2) ease of ventilation. The inflated ramped position provided greater ease of ventilation as compared to the neutral position (p = 0.0003). There was also a significant improvement in the glottic view in the ramped position (p = 0.04). Ease of intubation was perceived to be severely difficult among two, and overall use of the positioning device was found to be difficult among seven of the residents. The RAMP effectively positions morbidly obese patients in the HELP position. Ease of ventilation and laryngoscopic view were both improved with its use in this patient population.
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http://dx.doi.org/10.1007/s11695-009-9885-8DOI Listing
October 2010
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