Karsten Bartels

Hypoxia and inflammation are two sides of the same coin

Hypoxia and inflammation share an interdependent relationship (1). Many recent publications implicate hypoxia-elicited inflammation, or inflammation during hypoxic conditions in the outcomes of a wide array of human diseases (2). On the one hand, inflammatory disease states are frequently characterized by tissue hypoxia, or stabilization of hypoxia-dependent transcription factors, such as hypoxia-inducible factor (HIF) (3). For example, intestinal inflammation, such as occurs during inflammatory bowel disease, is characterized by the occurrence of severe hypoxia of the mucosal surface, and concomitant stabilization of HIF (4, 5). Stabilization of HIF1A during intestinal inflammation is caused by alterations in metabolic supply and demand ratios, particularly for oxygen, leading to “inflammatory hypoxia” (6). Similarly, lung inflammation, such as occurs during acute lung injury, is associated with metabolic alterations leading to the stabilization of HIF1A (7). On the other hand, disease conditions that are primarily caused by a lack of oxygen are characterized by secondary inflammatory changes. For example, ischemia and reperfusion injury is characterized by inflammatory responses that lead to subsequent organ dysfunction (8). The functional role of hypoxia-signaling and stabilization of HIFs during acute inflammatory or hypoxic disease states has been the focus of many recent studies. Surprisingly, many of these studies show that pharmacologic stabilization of HIF functions in an adaptive manner by increasing ischemia tolerance (9) and controlling excessive inflammation (10). Many of the studies have linked the anti-inflammatory effects of hypoxia-signaling to a transcriptional program that is under the control of HIF, where pharmacologic activators of HIFs provide tissue protection (11, 12). However, a recent study by Scholz et al. … [↵][1]1To whom correspondence should be addressed. E-mail: Holger.Eltzschig{at}UCDenver.edu. [1]: #xref-corresp-1-1

Opioid Use and Storage Patterns by Patients after Hospital Discharge following Surgery.

Introduction Opioid-based analgesic therapy represents a cornerstone of pain management after surgery. The recent rise in opioid sales and opioid overdoses suggests it is important to maximize the safety of opioid prescribing after surgery. Given that patients may live with other family members in the home, safe storage and appropriate disposal of excess opioids after hospital discharge are necessary to prevent unintended secondary exposures. Identifying characteristics of patients who are likely to be prescribed excess opioids after surgery may enable more targeted prescription practices and safety interventions. Our study aimed to elucidate patient-reported opioid use patterns and modes of home storage of opioids among patients discharged home after Cesarean section (C-section) and thoracic surgery. Specifically, we sought to identify characteristics of patients who reported using about half or more versus less of the opioids prescribed to them for use after hospital discharge. Methods For this cohort study, we developed a survey on quality of analgesia following hospital discharge, amounts of opioids taken relative to the amount prescribed, reasons for not taking all prescribed medications, and storage and disposal methods for leftover opioids. Adult patients, who had C-section or thoracic surgery at a tertiary academic medical center, were given a web-based self-administered survey after discharge. Descriptive statistics (means and standard deviations, proportions) were used to describe the study sample and survey results. Comparisons between patients who reported taking about half or more versus less of the opioids prescribed to them for use after hospital discharge were made using unpaired t-tests, Mann-Whitney tests, and Chi-square tests as appropriate. Results The majority (53%) of respondents after C-section (N = 30) reported taking either no or very few (less than 5) prescribed opioid pills; 83% reported taking half or less; and 17% of women, reported taking all or nearly all (5 or fewer pills left over) of their opioid prescription. In a cohort of patients after thoracic surgery (n = 31) 45% reported taking either no or very few (5 or less) prescribed opioid pills; 71% reported taking half or less; and 29% of patients reported taking all or nearly all (5 or fewer pills left over) of their opioid prescription. In both cohorts, use of opioids while hospitalized was higher in the group reporting using about half or more of prescribed opioids after discharge. Leftover opioids were stored in an unlocked location in 77% and 73% of cases following C-section and thoracic surgery, respectively. Conclusion Our findings from surveys in two distinct patient populations at a single academic medical center suggest that current opioid prescribing practices for pain management at hospital discharge following Cesarean section and thoracic surgery may not account for individual patients’ analgesic requirements. Excess opioid pills are commonly stored in unsecured locations and represent a potential source for non-medical opioid use and associated morbidity and mortality in patients and their families. Research to develop goal-directed and patient-centered post-discharge opioid prescription practices and encourage opioid safety practices after surgery is needed.

Perioperative Organ Injury

Despite the fact that a surgical procedure may have been performed for the appropriate indication and in a technically perfect manner, patients are threatened by perioperative organ injury. For example, stroke, myocardial infarction, acute respiratory distress syndrome, acute kidney injury, or acute gut injury are among the most common causes for morbidity and mortality in surgical patients. In the current review, the authors discuss the pathogenesis of perioperative organ injury, and provide select examples for novel treatment concepts that have emerged over the past decade. Indeed, the authors are of the opinion that research to provide mechanistic insight into acute organ injury and identification of novel therapeutic approaches for the prevention or treatment of perioperative organ injury represent the most important opportunity to improve outcomes of anesthesia and surgery.

Cardiac output monitoring: a contemporary assessment and review.

Objective:An increasing number of minimally or noninvasive devices are available to measure cardiac output in the critical care setting. This article reviews the underlying physical principles of these devices in addition to examining both animal and human comparative studies in an effort to allow clinicians to make informed decisions when selecting a device to measure cardiac output. Data Sources:Peer-reviewed manuscripts indexed in PubMed. Study Selection:A systematic search of the PubMed database for articles describing the use of cardiac output monitors yielded 1,526 sources that were included in the analysis. Data Extraction:From all published cardiac output monitoring studies reviewed, the animal model, number of independent measurements, and correlation between techniques was extracted. Data Synthesis:Comparative studies in animals and humans between devices designed for measurement of cardiac output and experimental reference standards indicate thermodilution and Doppler-based techniques to have acceptable accuracy across a wide range of hemodynamic conditions, with bioimpedance techniques being less accurate. Thermodilution devices are marginally more accurate than Doppler-based devices but suffer from slower response time, increased invasiveness, and require stable core temperatures, good operator technique, and a competent tricuspid valve. Doppler-based techniques are less invasive and offer beat-to-beat measurements and excellent trending ability, but are dependent on accurate beam alignment and knowledge of aortic cross-sectional area. Studies of newer devices, such as pulse contour analysis, partial rebreathing, and pulse wave velocity, are far less in number and are primarily based on comparisons with thermodilution-based cardiac output measurements. Studies show widely ranging results. Conclusion:Thermodilution is relatively accurate for cardiac output measurements in both animals and humans when compared to experimental reference standards. Doppler-based techniques appear to have similar accuracy as thermodilution pulmonary artery catheters. Bioimpedance, pulse contour, partial rebreathing, and pulse wave velocity-based devices have not been studied as rigorously; however, the majority of studies included in this analysis point towards decreased accuracy.

Neurocognitive outcomes after cardiac surgery.

Purpose of review To summarize recent studies of neurocognitive dysfunction after cardiac surgery, as well as to outline efforts and approaches toward advancing the field. Recent findings Observational studies have improved our understanding of the incidence and the trajectory of cognitive decline after cardiac surgery; however, the magnitude of this neurocognitive change remains controversial because of the inconsistent definitions and the lack of a gold-standard diagnostic modality. Nonetheless, physicians commonly see patients with functional and cognitive impairments after cardiac surgery, which utilize healthcare resources and impact quality of life. Novel approaches have utilized advanced neuroimaging techniques as well as innovative monitoring modalities to improve the efficiency of neuroprotective strategies during cardiac surgery. Summary Adverse cognitive and neurologic outcomes following cardiac surgery range from discrete neurocognitive deficits to severe neurologic injury such as stroke and even death. The elderly are at higher risk of suffering these outcomes and the public health dimension of this problem is expected to accelerate. Future studies should combine advanced neuroimaging with genomic, transcriptional, proteomic, and metabolomic profiling to improve our understanding of the pathophysiologic mechanisms and optimize the diagnosis, prevention, and treatment of neurocognitive injury.

Postoperative Pulmonary Complications, Early Mortality, and Hospital Stay Following Noncardiothoracic Surgery: A Multicenter Study by the Perioperative Research Network Investigators

Importance Postoperative pulmonary complications (PPCs), a leading cause of poor surgical outcomes, are heterogeneous in their pathophysiology, severity, and reporting accuracy. Objective To prospectively study clinical and radiological PPCs and respiratory insufficiency therapies in a high-risk surgical population. Design, Setting, and Participants We performed a multicenter prospective observational study in 7 US academic institutions. American Society of Anesthesiologists physical status 3 patients who presented for noncardiothoracic surgery requiring 2 hours or more of general anesthesia with mechanical ventilation from May to November 2014 were included in the study. We hypothesized that PPCs, even mild, would be associated with early postoperative mortality and use of hospital resources. We analyzed their association with modifiable perioperative variables. Exposure Noncardiothoracic surgery. Main Outcomes and Measures Predefined PPCs occurring within the first 7 postoperative days were prospectively identified. We used bivariable and logistic regression analyses to study the association of PPCs with ventilatory and other perioperative variables. Results This study included 1202 patients who underwent predominantly abdominal, orthopedic, and neurological procedures. The mean (SD) age of patients was 62.1 (13.8) years, and 636 (52.9%) were men. At least 1 PPC occurred in 401 patients (33.4%), mainly the need for prolonged oxygen therapy by nasal cannula (n = 235; 19.6%) and atelectasis (n = 206; 17.1%). Patients with 1 or more PPCs, even mild, had significantly increased early postoperative mortality, intensive care unit (ICU) admission, and ICU/hospital length of stay. Significant PPC risk factors included nonmodifiable (emergency [yes vs no]: odds ratio [OR], 4.47, 95% CI, 1.59-12.56; surgical site [abdominal/pelvic vs nonabdominal/pelvic]: OR, 2.54, 95% CI, 1.67-3.89; and age [in years]: OR, 1.03, 95% CI, 1.02-1.05) and potentially modifiable (colloid administration [yes vs no]: OR, 1.75, 95% CI, 1.03-2.97; preoperative oxygenation: OR, 0.86, 95% CI, 0.80-0.93; blood loss [in milliliters]: OR, 1.17, 95% CI, 1.05-1.30; anesthesia duration [in minutes]: OR, 1.14, 95% CI, 1.05-1.24; and tidal volume [in milliliters per kilogram of predicted body weight]: OR, 1.12, 95% CI, 1.01-1.24) factors. Conclusions and Relevance Postoperative pulmonary complications are common in patients with American Society of Anesthesiologists physical status 3, despite current protective ventilation practices. Even mild PPCs are associated with increased early postoperative mortality, ICU admission, and length of stay (ICU and hospital). Mild frequent PPCs (eg, atelectasis and prolonged oxygen therapy need) deserve increased attention and intervention for improving perioperative outcomes.

Inter-device differences in monitoring for goal-directed fluid therapy

PurposeGoal-directed fluid therapy is an integral component of many Enhanced Recovery After Surgery (ERAS) protocols currently in use. The perioperative clinician is faced with a myriad of devices promising to deliver relevant physiologic data to better guide fluid therapy. The goal of this review is to provide concise information to enable the clinician to make an informed decision when choosing a device to guide goal-directed fluid therapy.Principal findingsThe focus of many devices used for advanced hemodynamic monitoring is on providing measurements of cardiac output, while other, more recent, devices include estimates of fluid responsiveness based on dynamic indices that better predict an individual’s response to a fluid bolus. Currently available technologies include the pulmonary artery catheter, esophageal Doppler, arterial waveform analysis, photoplethysmography, venous oxygen saturation, as well as bioimpedance and bioreactance. The underlying mechanistic principles for each device are presented as well as their performance in clinical trials relevant for goal-directed therapy in ERAS.ConclusionsThe ERAS protocols typically involve a multipronged regimen to facilitate early recovery after surgery. Optimizing perioperative fluid therapy is a key component of these efforts. While no technology is without limitations, the majority of the currently available literature suggests esophageal Doppler and arterial waveform analysis to be the most desirable choices to guide fluid administration. Their performance is dependent, in part, on the interpretation of dynamic changes resulting from intrathoracic pressure fluctuations encountered during mechanical ventilation. Evolving practice patterns, such as low tidal volume ventilation as well as the necessity to guide fluid therapy in spontaneously breathing patients, will require further investigation.RésuméObjectifLa réanimation liquidienne ciblée fait partie intégrale de nombreux protocoles de récupération rapide après une chirurgie (RRAC ou ERAS: Enhanced Recovery After Surgery) utilisés à l’heure actuelle. Le clinicien en périopératoire est confronté à une myriade de dispositifs promettant de fournir des données physiologiques pertinentes pour mieux guider la réanimation liquidienne. L’objectif de cet exposé de synthèse est de fournir une information concise permettant au clinicien de prendre une décision éclairée sur le choix d’un dispositif devant guider la réanimation liquidienne ciblée.Constatations principalesL’objectif de nombreux dispositifs utilisés pour le monitorage avancé de l’hémodynamie consiste à fournir des mesures de débit cardiaque tandis que d’autres, plus récents, incluent une estimation de la réponse liquidienne en fonction d’indices dynamiques qui prédisent mieux la réponse individuelle à un bolus liquidien. Les technologies actuellement disponibles incluent le cathétérisme de l’artère pulmonaire, le Doppler œsophagien, l’analyse de la courbe artérielle, la photopléthysmographie, la saturation veineuse en oxygène, ainsi que la bioimpédance et la bioréactance. Les principes mécanistes sous-jacents de chaque dispositif sont présentés, ainsi que leurs performances au cours d’essais cliniques pertinents pour la réanimation liquidienne ciblée dans le cadre de la RRAC.ConclusionsLes protocoles RRAC impliquent habituellement un schéma thérapeutique multiaxes pour faciliter la récupération rapide après chirurgie. L’optimisation périopératoire de la réanimation liquidienne est un élément clé de ces efforts. Bien qu’il n’y ait pas de technologies dénuées de limites, l’essentiel des publications actuellement disponibles suggère que le Doppler œsophagien et l’analyse des courbes artérielles sont les choix les plus souhaitables pour guider l’administration de liquides. Leur performance dépend, en partie, de l’interprétation des modifications dynamiques résultant de la fluctuation de la pression intrathoracique observée au cours de la ventilation mécanique. Les schémas évolutifs de pratique, tels que la ventilation à petit volume courant ainsi que la nécessité de guider la thérapie liquidienne chez des patients respirant spontanément, nécessiteront des études complémentaires.

Rational fluid management in today's ICU practice

Intravenous fluid therapy has evolved significantly over time. From the initial report of the first intravenous administration of sodium-chloride-based solution to the development of goal-directed fluid therapy using novel dynamic indices, efforts have focused on improving patient outcomes. The goal of this review is to provide a brief overview of current concepts for intravenous fluid administration in the ICU. Results of recently published clinical trials suggesting harmful effects of starch-based solutions on critically ill patients are discussed. Concepts for goal-directed fluid therapy and new modalities for the assessment of fluid status as well as for the prediction of responsiveness to different interventions will continue to emerge. Advances in technology will have to be critically evaluated for their ability to improve outcomes in different clinical scenarios.

Correction: Rational fluid management in today's ICU practice

*Correspondence: tong.gan@dm.duke.edu 1Department of Anesthesiology, Box 3094, Suite 5670B, Duke University Medical Center, Durham, NC 27710, USA Full list of author information is available at the end of the article doi:10.1186/cc12771 Cite this article as: Bartels K, et al.: Correction: Rational fl uid management in today’s ICU practice. Critical Care 2013, 17(Suppl 1):S10. Bartels et al. Critical Care 2013, 17(Suppl 1):S10 http://ccforum.com/content/17/S1/S9

Effects of Deep Hypothermic Circulatory Arrest on the Blood Brain Barrier in a Cardiopulmonary Bypass Model – A Pilot Study

BACKGROUND Neurologic injury is common after cardiac surgery and disruption of the blood brain barrier (BBB) has been proposed as a contributing factor. We sought to study BBB characteristics in a rodent model of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). METHODS Adult rats were subjected to CPB/DHCA or to sham surgery. Analysis included Western blotting of relevant BBB proteins in addition to in vivo brain magnetic resonance imaging (MRI) with a clinically used low-molecular contrast agent. RESULTS While quantitative analysis of BBB proteins revealed similar expression levels, MRI showed evidence of BBB disruption after CPB/DHCA compared to sham surgery. CONCLUSIONS Combining molecular BBB analysis and MRI technology in a rodent model is a highly translatable approach to study adverse neurologic outcomes following CPB/DHCA.