Intra-abdominal hypertension and abdominal compartment syndrome: a current review.

PURPOSE OF REVIEW: Intra-abdominal hypertension (IAH) and its deleterious effects are present in at least one-third of ICU patients. Increased recognition of IAH has led to significant reduction in the incidence of abdominal compartment syndrome (ACS). Many questions remain regarding what therapeutic interventions truly reduce morbidity and mortality associated with IAH/ACS. Recent research sheds new light on the effects of IAH in individual organ systems and unique disease states. This paper will review recent research in IAH/ACS recognition, treatment, and management. RECENT FINDINGS: Recent research on IAH/ACS includes an improved understanding of the prevalence of IAH/ACS and confirmation of its independent association with organ failure. Specifically, new research adds clarity to the effects of IAH/ACS on individual organ systems and specific disease states. These results combine to improve the clinical ability to diagnose, monitor, and treat IAH/ACS. SUMMARY: There is significant research on the broad impact of IAH/ACS in the ICU setting. Focus on IAH/ACS has gone beyond the purview of intensivists and surgeons to include outstanding work by specialists in multiple sub-specialties. These advances have generated improvements in current treatment algorithms. We review recent IAH/ACS literature and have categorized the most pertinent results into organ system-specific contributions.

Do we have the guts to go? The abdominal compartment, intra-abdominal hypertension, the human microbiome and exploration class space missions.

Humans are destined to explore space, yet critical illness and injury may be catastrophically limiting for extraterrestrial travel. Humans are superorganisms living in symbiosis with their microbiomes, whose genetic diversity dwarfs that of humans. Symbiosis is critical and imbalances are associated with disease, occurring within hours of serious illness and injury. There are many characteristics of space flight that negatively influence the microbiome, especially deep space itself, with its increased radiation and absence of gravity. Prolonged weightlessness causes many physiologic changes that are detrimental; some resemble aging and will adversely affect the ability to tolerate critical illness or injury and subsequent treatment. Critical illness-induced intra-abdominal hypertension (IAH) may induce malperfusion of both the viscera and microbiome, with potentially catastrophic effects. Evidence from animal models confirms profound IAH effects on the gut, namely ischemia and disruption of barrier function, mechanistically linking IAH to resultant organ dysfunction. Therefore, a pathologic dysbiome, space-induced immune dysfunction and a diminished cardiorespiratory reserve with exacerbated susceptibility to IAH, imply that a space-deconditioned astronaut will be vulnerable to IAH-induced gut malperfusion. This sets the stage for severe gut ischemia and massive biomediator generation in an astronaut with reduced cardiorespiratory/immunological capacity. Fortunately, experiments in weightless analogue environments suggest that IAH may be ameliorated by conformational abdominal wall changes and a resetting of thoracoabdominal mechanics. Thus, review of the interactions of physiologic changes with prolonged weightlessness and IAH is required to identify appropriate questions for planning exploration class space surgical care.

L'humanité est à l'aube d'une nouvelle ère d'exploration spatiale, mais le risque de maladies et blessures graves pourrait restreindre de manière catastrophique le potentiel des voyages dans l'espace. L'être humain est un superorganisme vivant en symbiose avec son microbiote, dont la diversité génétique éclipse celle de l'hôte. Cette symbiose est essentielle : tout déséquilibre est associé à une dégradation de l'état de santé dans les heures suivant l'occurrence d'une blessure ou d'une maladie grave. Bon nombre de caractéristiques propres au vol spatial ont des répercussions négatives sur le microbiote; l'espace lointain présente des dangers particuliers en raison de l'exposition accrue au rayonnement et de l'absence de gravité. L'exposition prolongée à l'apesanteur cause une myriade de changements physiologiques nuisant à la santé. Certains ressemblent à des processus de vieillissement et réduiront la capacité à tolérer une blessure ou une maladie grave et son traitement. L'hypertension intra-abdominale (HIA) causée par une maladie grave peut réduire la perfusion des viscères et du microbiote, ce qui peut avoir des conséquences catastrophiques. Des études sur modèle animal ont confirmé les effets profondément délétères de l'HIA sur les intestins par l'apparition d'une ischémie et une altération de la barrière intestinale; cette découverte permettrait d'établir un lien mécanistique entre l'HIA et la défaillance d'organes résultante. Par conséquent, une dysbiose pathologique, associée à un dysfonctionnement immunitaire en apesanteur et à une réduction de la réserve cardiorespiratoire accompagnée d'une exacerbation de la susceptibilité à l'HIA, pourrait signifier qu'un astronaute exposé à l'effet déconditionnant de l'apesanteur serait vulnérable aux problèmes de perfusion de l'intestin découlant de l'HIA. Ce problème pourrait à son tour mener à une ischémie intestinale grave et à une production massive de biomédiateurs chez un astronaute présentant déjà une capacité cardiorespiratoire et immunitaire réduite. Heureusement, des expériences dans des environnements simulant l'apesanteur semblent indiquer que les effets de l'HIA pourraient être contrés par des changements conformationnels de la paroi abdominale et un rétablissement de la mécanique thoracoabdominale. Par conséquent, un examen des interactions des changements physiologiques associés à un état d'apesanteur prolongé et à l'HIA est requis pour déterminer les questions à poser afin de planifier adéquatement les soins chirurgicaux en contexte d'exploration spatiale.

Incidence, Risk Factors, and Outcomes of Intra-Abdominal Hypertension in Critically Ill Patients-A Prospective Multicenter Study (IROI Study).

OBJECTIVES: To identify the prevalence, risk factors, and outcomes of intra-abdominal hypertension in a mixed multicenter ICU population. DESIGN: Prospective observational study. SETTING: Fifteen ICUs worldwide. PATIENTS: Consecutive adult ICU patients with a bladder catheter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four hundred ninety-one patients were included. Intra-abdominal pressure was measured a minimum of every 8 hours. Subjects with a mean intra-abdominal pressure equal to or greater than 12 mm Hg were defined as having intra-abdominal hypertension. Intra-abdominal hypertension was present in 34.0% of the patients on the day of ICU admission (159/467) and in 48.9% of the patients (240/491) during the observation period. The severity of intra-abdominal hypertension was as follows: grade I, 47.5%; grade II, 36.6%; grade III, 11.7%; and grade IV, 4.2%. The severity of intra-abdominal hypertension during the first 2 weeks of the ICU stay was identified as an independent predictor of 28- and 90-day mortality, whereas the presence of intra-abdominal hypertension on the day of ICU admission did not predict mortality. Body mass index, Acute Physiology and Chronic Health Evaluation II score greater than or equal to 18, presence of abdominal distension, absence of bowel sounds, and positive end-expiratory pressure greater than or equal to 7 cm H2O were independently associated with the development of intra-abdominal hypertension at any time during the observation period. In subjects without intra-abdominal hypertension on day 1, body mass index combined with daily positive fluid balance and positive end-expiratory pressure greater than or equal to 7 cm H2O (as documented on the day before intra-abdominal hypertension occurred) were associated with the development of intra-abdominal hypertension during the first week in the ICU. CONCLUSIONS: In our mixed ICU patient cohort, intra-abdominal hypertension occurred in almost half of all subjects and was twice as prevalent in mechanically ventilated patients as in spontaneously breathing patients. Presence and severity of intra-abdominal hypertension during the observation period significantly and independently increased 28- and 90-day mortality. Five admission day variables were independently associated with the presence or development of intra-abdominal hypertension. Positive fluid balance was associated with the development of intra-abdominal hypertension after day 1.

Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients.

RATIONALE: Mechanically ventilated intensive care unit (ICU) patients are frequently managed using a continuous-infusion sedative. Although recent guidelines suggest avoiding benzodiazepines for sedation, this class of drugs is still widely used. There are limited data comparing sedative agents in terms of clinical outcomes in an ICU setting. OBJECTIVES: Comparison of propofol to midazolam and lorazepam in adult ICU patients. METHODS: Data were obtained from a multicenter ICU database (2003-2009). Patient selection criteria included age greater than or equal to 18 years, single ICU admission with single ventilation event (>48 h), and treatment with continuously infused sedation (propofol, midazolam, or lorazepam). Propensity score analysis (1:1) was used and mortality measured. Cumulative incidence and competing risk methodology were used to examine time to ICU discharge and ventilator removal. MEASUREMENTS AND MAIN RESULTS: There were 2,250 propofol-midazolam and 1,054 propofol-lorazepam matched patients. Hospital mortality was statistically lower in propofol-treated patients as compared with midazolam- or lorazepam-treated patients (risk ratio, 0.76; 95% confidence interval [CI], 0.69-0.82 and risk ratio, 0.78; 95% CI, 0.68-0.89, respectively). Competing risk analysis for 28-day ICU time period showed that propofol-treated patients had a statistically higher probability for ICU discharge (78.9% vs. 69.5%; 79.2% vs. 71.9%; P < 0.001) and earlier removal from the ventilator (84.4% vs. 75.1%; 84.3% vs. 78.8%; P < 0.001) when compared with midazolam- and lorazepam-treated patients, respectively. CONCLUSIONS: In this large, propensity-matched ICU population, patients treated with propofol had a reduced risk of mortality and had both an increased likelihood of earlier ICU discharge and earlier discontinuation of mechanical ventilation.

Urinary catheter monitoring of intra-abdominal pressure after major abdominal surgery, a cost-benefit analysis.

OBJECTIVE: To estimate costs and benefits associated with measurement of intra-abdominal pressure (IAP). METHODS: We built a cost-benefit analysis from the hospital facility perspective and time horizon limited to hospitalization for patients undergoing major abdominal surgery for the intervention of urinary catheter monitoring of IAP. We used real-world data estimating the likelihood of intra-abdominal hypertension (IAH), abdominal compartment syndrome (ACS), and acute kidney injury (AKI) requiring renal replacement therapy (RRT). Costs included catheter costs (estimated $200), costs of additional intensive care unit (ICU) days from IAH and ACS, and costs of CRRT. We took the preventability of IAH/ACS given early detection from a trial of non-surgical interventions in IAH. We evaluated uncertainty through probabilistic sensitivity analysis and the effect of individual model parameters on the primary outcome of cost savings through one-way sensitivity analysis. RESULTS: In the base case, urinary catheter monitoring of IAP in the perioperative period of major abdominal surgery had 81% fewer cases of IAH of any grade, 64% fewer cases of AKI, and 96% fewer cases of ACS. Patients had 1.5 fewer ICU days attributable to IAH (intervention 1.6 days vs. control of 3.1 days) and a total average cost reduction of $10,468 (intervention $10,809, controls $21,277). In Monte Carlo simulation, 86% of 1,000 replications were cost-saving, for a mean cost savings of $10,349 (95% UCI $8,978, $11,720) attributable to real-time urinary catheter monitoring of intra-abdominal pressure. One-way factor analysis showed the pre-test probability of IAH had the largest effect on cost savings and the intervention was cost-neutral at a prevention rate as low as 2%. CONCLUSIONS: In a cost-benefit model using real-world data, the potential average in-hospital cost savings for urinary catheter monitoring of IAP for early detection and prevention of IAH, ACS, and AKI far exceed the cost of the catheter.

Fluid Management, Intra-Abdominal Hypertension and the Abdominal Compartment Syndrome: A Narrative Review.

BACKGROUND: General pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear. OBJECTIVES: This review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS). METHODS: We performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH. RESULTS: We identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality. CONCLUSIONS: Current evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.

Implementation of an enoxaparin protocol for venous thromboembolism prophylaxis in obese surgical intensive care unit patients.

BACKGROUND: Venous thromboembolism (VTE) is a serious health care issue that affects a large number of people. Few standards exist for delineating the optimal dosing strategy for VTE prevention in obese patients, especially in the setting of major surgery or trauma. OBJECTIVE: To document the efficacy of a surgical intensive care unit (SICU)-specific, weight-based dosing protocol of enoxaparin 0.5 mg/kg given subcutaneously every 12 hours for VTE prophylaxis in morbidly obese (defined as body mass index [BMI] ≥35 kg/m(2) or weight ≥150 kg) SICU patients, using peak anti-factor Xa levels to determine therapeutic endpoints. METHODS: Data were collected retrospectively in an academic, university-based SICU on 23 morbidly obese patients who received weight-based enoxaparin for VTE prophylaxis from December 1, 2008, through June 30, 2010. RESULTS: A weight-based dosage range of enoxaparin 50-120 mg twice daily (median 60) was given to 23 patients. The mean BMI was 46.4 kg/m(2). The initial mean anti-factor Xa level (measured after the third dose) was 0.34 IU/mL (range 0.20-0.59). Patients received an average of 18 doses. Two cases required an increase or decrease in dosage based on anti-factor Xa levels. Morbidity related to this dosing included a single event of minor endotracheal bleeding and a single deep vein thrombosis that was likely present prior to treatment. CONCLUSIONS: Weight-based dosing with enoxaparin in morbidly obese SICU patients was effective in achieving anti-factor Xa levels within the appropriate prophylactic range. This regimen reduced the rate of VTE below expected levels and no additional adverse effects were reported.

Intra-abdominal hypertension and hypoxic respiratory failure together predict adverse outcome - A sub-analysis of a prospective cohort.

PURPOSE: To assess whether the combination of intra-abdominal hypertension (IAH, intra-abdominal pressure ≥ 12 mmHg) and hypoxic respiratory failure (HRF, PaO2/FiO2 ratio < 300 mmHg) in patients receiving invasive ventilation is an independent risk factor for 90- and 28-day mortality as well as ICU- and ventilation-free days. METHODS: Mechanically ventilated patients who had blood gas analyses performed and intra-abdominal pressure measured, were included from a prospective cohort. Subgroups were defined by the absence (Group 1) or the presence of either IAH (Group 2) or HRF (Group 3) or both (Group 4). Mixed-effects regression analysis was performed. RESULTS: Ninety-day mortality increased from 16% (Group 1, n = 50) to 30% (Group 2, n = 20) and 27% (Group 3, n = 100) to 49% (Group 4, n = 142), log-rank test p < 0.001. The combination of IAH and HRF was associated with increased 90- and 28-day mortality as well as with fewer ICU- and ventilation-free days. The association with 90-day mortality was no longer present after adjustment for independent variables. However, the association with 28-day mortality, ICU- and ventilation-free days persisted after adjusting for independent variables. CONCLUSIONS: In our sub-analysis, the combination of IAH and HRF was not independently associated with 90-day mortality but independently increased the odds of 28-day mortality, and reduced the number of ICU- and ventilation-free days.

Synthesis and SAR of pyridazinone-substituted phenylalanine amide alpha4 integrin antagonists.

Structural modification and cellular adhesion inhibition activities of pyridazinone-substituted phenylalanine amide alpha(4) integrin antagonists are described. Functionality requirements for the arylamide moiety and the carboxylic acid group were demonstrated. The study also revealed novel structure-activity relationships (SAR) for arylated pyridazinones. A correlation between bioavailability and permeability was also explored. A selected compound showed effectiveness in a mouse leukocytosis study.

Reproducibility of bladder pressure measurements in critically ill patients.

OBJECTIVE: Intra-abdominal hypertension is an independent cause of multiorgan failure and directly effects other physiological measurements, making it an important factor in the management of critically ill patients, but no clinical studies have investigated the reproducibility of intra-abdominal pressure (IAP) measurement to ensure diagnostic accuracy. This study evaluated the intraobserver and interobserver variability of bladder pressure measurements. DESIGN AND SETTING: Prospective, observational study in a university-based adult surgical intensive care unit. PATIENTS: Critically ill patients undergoing intra-abdominal pressure readings, measured by nursing staff. MEASUREMENTS AND RESULTS: The study compared patient IAP measurements obtained by the same nurse (intraobserver variation) and between two different nurses (interobserver variation) in critical care patients with clinical indications for IAP monitoring. Data related to the nursing technique and performance were observed and collected for each IAP measurement obtained. Good correlation of bladder pressure measurements between the same and different individuals was found. Intraobserver and interobserver Pearson's correlations for measured IAP were 0.934 and 0.950, respectively. A unit protocol for IAP measurement standardization was modified based on observational data collected. CONCLUSIONS: Intra-abdominal pressure can be accurately and reliably measured in critically ill patients by utilizing a standardized measurement device combined with a standardized clinical protocol.

Treatment patterns and clinical characteristics of patients with type 2 diabetes mellitus according to body mass index: findings from an electronic medical records database.

OBJECTIVE: This study evaluated relationships between glycaemic control, body mass index (BMI), comorbidities and pharmacological treatment in patients with type 2 diabetes mellitus (T2D). RESEARCH DESIGN AND METHODS: This was a retrospective, cross-sectional analysis of Quintiles electronic medical records research data (study period 1 October 2013-30 September 2014). Eligibility included age ≥18 years, T2D diagnosis, and at least one available BMI measurement. RESULTS: The study included 626 386 patients (mean age, 63.8 year; 51.3% female; 78.5% white; 62.6%, BMI ≥30 kg/m2). A1c data were available for 414 266 patients. The proportion of patients with good glycaemic control (A1c ≤6.5) decreased as BMI category increased, ranging from 40.1% of patients with BMI <30% to 30.1% of patients with BMI ≥40. The proportions of patients with poor glycaemic control (A1c >8% and A1c ≥9%) increased with increasing BMI category. Oral antidiabetic drugs (OAD) were the most frequently used (54.4% of patients with A1c values). Among patients using insulin-based therapy, 50% had an A1c ≥8% and 29% had an A1c ≥9% regardless of concomitant OAD or glucagon-like peptide 1 receptor agonist use. Among patients using three or more OADs, 34.3% and 16.1% had A1c values ≥8% and ≥9%, respectively. There was no common trend observed for changes in the proportion of patients with T2D-related comorbidities according to BMI category. The most notable trend was a 7.6% net increase in the percentage of patients with hypertension from BMI <30 to BMI ≥40. CONCLUSIONS: This large dataset provides evidence that roughly one out of four patients with T2D is not well controlled, and the prevalence of poor glycaemic control increases as BMI increases.

Synthesis and biological evaluation of novel pyridazinone-based alpha4 integrin receptor antagonists.

A novel series of pyridazinone-functionalized phenylalanine analogues was prepared and evaluated for inhibition of cellular adhesion mediated by alpha4beta1/VCAM-1 and alpha4beta7/MAdCAM-1 interactions. Concise syntheses were developed and applied for exploration of structure-activity relationships pertaining to the pyridazinone ring as well as the N-acyl phenylalanine scaffold. Potent dual antagonists of alpha4beta1 and alpha4beta7 were generated from an amide subseries; antagonists selective for alpha4beta7 were identified from urea and carbamate-based subseries. The pharmacokinetic properties of selected members of the series have been determined in rats and demonstrate that the use of ester prodrugs and alterations to the amide linkage can lead to improved oral bioavailability in this series. An alpha4beta7-selective member of the carbamate subseries (36c), upon oral administration, demonstrated in vivo efficacy in the mouse DSS colitis model.

Effects of Age on Glycemic Control in Patients With Type 2 Diabetes Treated with Insulin Detemir: A Post-Hoc Analysis of the PREDICTIVE™ 303 Study.

BACKGROUND: This post-hoc sub-analysis investigated whether age (<65 years vs ≥65 years) affects glycemic control or hypoglycemic risk in patients with type 2 diabetes mellitus (T2DM) treated with once-daily insulin detemir. METHODS: This was a 26-week, randomized, open-label, phase IV trial involving 2812 patients at 1083 predominantly primary care sites throughout the United States, of which 541 were designated for investigator-led insulin titration. The main efficacy measure was change in HbA1c (A1C) from baseline to Week 26. Patients were stratified by age in the sites designated for the investigator-led titration of insulin detemir. Safety measures included adverse events and change in hypoglycemic event rates from baseline to Week 26. RESULTS: At Week 26, mean A1C and fasting plasma glucose decreased in both groups, but mean differences in change from baseline were not significant between groups. Within the group ≥65 years, significant reductions occurred for all daytime hypoglycemia, but there was no significant change from baseline in the other categories. In the group <65 years, reductions from baseline were significant for all hypoglycemic event categories. Changes in hypoglycemia rates from baseline were not significantly different between the age groups and there was no weight increase in either age group. CONCLUSIONS: This analysis demonstrates that insulin detemir has similar efficacy and safety profiles for patients with T2DM ≥65 years compared with <65 years when treated via an investigator-led algorithm.

Longitudinal Changes in Medical Services and Related Costs in a Single Cohort of Patients Newly Diagnosed With Type 2 Diabetes, 2006 to 2012.

PURPOSE: Documenting diabetes treatment patterns and associated costs over time is an important step in gauging the medical and economic impact of current treatment guidelines in a real-world setting. This study was designed to assess changes in medication treatment patterns, health care costs, and comorbidities over a 6-year period after a new diagnosis of type 2 diabetes mellitus (T2DM). This analysis is the first of its kind to observe, over time, a single US cohort of patients newly diagnosed with T2DM. METHODS: This study was a longitudinal assessment of changes in medical services and comorbidities for a single cohort (N = 35,017) of adults newly diagnosed with T2DM in 2006 using claims data from Truven Health Analytics MarketScan(®) databases. Prevalence of diabetes-related comorbidities and utilization/costs of inpatient/outpatient services and medications were analyzed annually for the index (diagnosis) year (Y1) through year 6 (Y6) postindex. Costs were adjusted to 2012 dollars. FINDINGS: From Y1 to Y6, increased prevalence was noted for several T2DM-associated comorbidities: cerebrovascular disease (13%-21%), peripheral vascular disease (3%-10%), nephropathy (3%-13%), and retinopathy (4%-14%). All-cause costs of inpatient and outpatient services and medications were analyzed for the index year (Y1) through Y6 postindex (adjusted to 2012 dollars). Total health care utilization costs (services plus drugs) increased by 33.3% from Y1 ($329.8 million) to Y6 ($439.5 million). Inpatient costs across the entire cohort increased 19.3% from Y1 ($49.8 million; $1421/patient) to Y6 ($59.4 million; $1695/patient) but increased 46.6% among utilizers, despite a decline in inpatient utilizers (7.3% to 5.9% of patients). The percentage of outpatient services utilizers remained stable (Y1, 98.2%; Y6, 97.2%), but total visits increased by 9.1%. Costs of outpatient services increased by 32.5%, from $145 million (Y1) to $192 million (Y6). Total drug costs increased from $101.5 million (Y1) to $114.7 million (Y6) but accounted for a smaller percentage of all health care costs in Y6 versus Y1 (26.1% vs 30.7%). Antidiabetes drugs accounted for a small percentage of overall costs in both Y1 (3.6%) and Y6 (5.3%). IMPLICATIONS: Overall, we found evidence of increasing comorbidities paralleled by large increases in costs for medical services but less for prescriptions. These findings confirm a need for aggressive diabetes management to slow disease progression and minimize comorbidity and economic burdens of the disease.

Decreasing incidence of type 2 diabetes mellitus in the United States, 2007-2012: Epidemiologic findings from a large US claims database.

AIMS: To explore epidemiological trends in type 2 diabetes mellitus (T2D) in the US between 2007 and 2012 using a large US claims database, with a particular focus on demographics, prevalence, newly-diagnosed cases, and comorbidities. METHODS: Truven Health MarketScan® Databases were used to identify patients with claims evidence of T2D in the years 2007 and 2012. Newly-diagnosed T2D was characterized by an absence of any T2D claims or related drug claims for 6months preceding the index claim. Demographic and comorbidity characteristics of the prevalent and new-onset T2D groups were compared and analyzed descriptively for trends over time. RESULTS: The overall prevalence of T2D remained stable from 2007 (1.24 million cases/15.07 million enrolled; 8.2%) to 2012 (2.04 million cases/24.52 million enrolled; 8.3%), while the percentage of newly-diagnosed cases fell dramatically from 2007 (152,252 cases; 1.1%) to 2012 (147,011 cases; 0.65%). The mean age of patients with prevalent T2D was similar in 2007 (60.6y) and 2012 (60.0y), while the mean age of newly-diagnosed T2D patients decreased by 3years from 2007 (57.7y) to 2012 (54.8y). Hypertension and hyperlipidemia were the most common comorbidities, evident in 50-75% of T2D patients, and increased markedly from 2007 to 2012 in both prevalent and new-onset T2D populations. Cardiovascular disease decreased slightly in prevalent (-0.9%) and new-onset (-2.8%) cases. CONCLUSIONS: This large US health claims database analysis suggests stabilization in prevalence and declining incidence of T2D over a recent 5-year period, a downward shift in age at T2D diagnosis, but increases in several comorbidities.

Critical care medicine training and certification for emergency physicians.

Demand for critical care services is increasing. Unless the supply of intensivists increases, critically ill patients will not have access to intensivists. Recent critical care society recommendations include increased graduate medical education support and expansion of the J-1 visa waiver program for foreign medical graduates. This article proposes additional recommendations, based on strengthening the relationship between emergency medicine and critical care medicine. Critical care is a continuum that includes out-of-hospital, emergency department (ED), and ICU care teams. Both emergency medicine and critical care medicine require expertise in treating life-threatening acute illness, with many critically ill patients often presenting first to the ED. Increased patient volumes and acuity have resulted in longer ED lengths of stay and more critical care delivery in the ED. However, the majority of critical care medicine fellowships do not accept emergency medicine residents, and those who do successfully complete a fellowship do not have access to a US certification examination in critical care medicine. Despite these barriers, interest in critical care medicine training among emergency physicians is increasing. Dual emergency medicine- and critical care medicine-trained physicians will not only help alleviate the intensivist shortage but also strengthen critical care delivery in the ED and facilitate coordination at the ED-ICU interface. We therefore propose that all accreditation bodies work cooperatively to create a route to critical care medicine certification for emergency physicians who complete a critical care fellowship.

Management of abdominal sepsis--a paradigm shift?

The abdomen is the second most common source of sepsis and secondary peritonitis. The most common causes of abdominal sepsis are perforation, ischemic necrosis or penetrating injury to the abdominal viscera. Management consists of control of the infection source, restoration of gastrointestinal tract (GI) function, systemic antimicrobial therapy and support of organ function. Mortality after secondary peritonitis is still high. Excluding patient-related factors such as age or co-morbidities that can not be influenced at the time of intervention, delay to surgical intervention and inability to obtain source control are the main determinants of outcome. In patients with severe physiological derangement or difficult intraperitoneal conditions, where a prolonged operation and complete anatomical repair may not be possible or appropriate, it is becoming increasingly popular to utilize a damage control strategy with abbreviated laparotomy and planned reoperations. The main components of damage control laparotomy for secondary peritonitis are postponing the reconstruction of intestinal anastomoses to a second operation (deferred anastomosis) and leaving the abdomen open with some form of temporary abdominal closure (TAC). Advances in the management techniques of the open abdomen and new negative pressure-based TAC-devices have significantly reduced the previously observed prohibitive morbidity associated with open abdomens. These advancements have led to current fascial closure rates after TAC approaching 90%. The cornerstones of appropriate antimicrobial therapy are the timing, spectrum and dosing of antibiotics. Enteral nutrition should be started as soon as possible in hemodynamically stable patients but withheld when the patient is on a significant dose of vasopressors or whenever GI hypoperfusion is suspected. Timely source control with appropriate use of antimicrobial agents and early intensive care offers the best chance of survival for patients with abdominal sepsis. The introduction of the concept of damage control to the management of secondary peritonitis represents a paradigm shift in the same way as in management of major trauma. Although limited and repeated surgical interventions have been shown to be safe, the actual benefits need to be demonstrated in controlled studies.

Historical cohort analysis of treatment patterns for patients with type 2 diabetes initiating metformin monotherapy.

OBJECTIVE: To describe treatment regimen changes of patients with type 2 diabetes mellitus (T2DM) initiating metformin monotherapy, and assess factors associated with those changes 12 months post-initiation. METHODS: Retrospective cohort analysis of medical, pharmacy and laboratory claims of 17,527 Medicare Advantage (MAPD) Humana members aged 18-89, who had ≥1 medical claim with primary diagnosis or ≥2 medical claims with secondary diagnosis of T2DM (ICD-9-CM code 250.x0 or 250.x2) who filled an initial prescription for metformin (GPI code 2725) between 1 January 2008 and 30 September 2011. The main outcome measure was change in metformin monotherapy during the 12 months following initiation. Factors associated with treatment changes during follow-up were examined using Cox proportional hazards regression models. RESULTS: Fifty-nine percent of patients (mean age 69.6 years) remained on metformin monotherapy with no changes. Discontinuation was the most common treatment change (33%), followed by addition (5%), and switching (2%) to other antidiabetics. Of patients who discontinued treatment (median time to discontinuation = 90 days), 61% did not reinitiate any diabetic treatment during the follow-up period. Among patients who added or switched to other antidiabetics, sulfonylureas were the most common addition or replacement agent. Predictors of discontinuation were being female, Black or Hispanic, low-income subsidy eligible, having higher initial out-of-pocket metformin costs, or a diagnosis of depression. Discontinuation was less likely during follow-up if patients had higher pre-index pill burdens or records of a pre-index A1C screening test. A higher risk of discontinuation was observed for patients with low baseline A1C. One study limitation was that exact discontinuation dates could not be determined using claims. CONCLUSIONS: The findings suggest that gender, race, ethnicity, depression, and low income status were contributory factors to metformin discontinuation. More intensive monitoring and treatment adjustments may be warranted for patients newly initiated on metformin. This could ultimately improve morbidity, mortality, and costs associated with poor glycemic control.

Intra-abdominal hypertension and abdominal compartment syndrome in burns, obesity, pregnancy, and general medicine.

Intra-abdominal hypertension (IAH) is an important contributor to early organ dysfunction in trauma and sepsis. However, relatively little is known about the impact of intra-abdominal pressure (IAP) in general internal medicine, pregnant patients, and those with obesity or burns. The aim of this paper is to review the pathophysiologic implications and treatment options for IAH in these specific situations. A MEDLINE and PubMed search was performed and the resulting body-of-evidence included in the current review on the basis of relevance and scientific merit. There is increasing awareness of the role of IAH in different clinical situations. Specifically, IAH will develop in most (if not all) severely burned patients, and may contribute to early mortality. One should avoid over-resuscitation of these patients with large volumes of fluids, especially crystalloids. Acute elevations in IAP have similar effects in obese patients compared to non-obese patients, but the threshold IAP associated with organ dysfunction may be higher. Chronic elevations in IAP may, in part, be responsible for the pathogenesis of obesity-related co-morbid conditions such as hypertension, pseudotumor cerebri, pulmonary dysfunction, gastroesophageal reflux disease, and abdominal wall hernias. At the bedside, measuring IAP and considering IAH in all critical maternal conditions is essential, especially in preeclampsia/eclampsia where some have hypothesized that IAH may have an additional role. IAH in pregnancy must take into account the precautions for aorto-caval compression and has been associated with ovarian hyperstimulation syndrome. Recently, IAP has been associated with the cardiorenal dilemma and hepatorenal syndrome, and this has led to the recognition of the polycompartment syndrome. In conclusion, IAH and ACS have been associated with several patient populations beyond the classical ICU, surgical, and trauma patients. In all at risk conditions the focus should be on the early recognition of IAH and prevention of ACS. Patients at risk for IAH should be identified early through measurements of IAP. Appropriate actions should be taken when IAP increases above 15 mm Hg, especially if pressures reach above 20 mm Hg with new onset organ failure. Although non-operative measures come first, surgical decompression must not be delayed if these fail. Percutaneous drainage of ascites is a simple and potentially effective tool to reduce IAP if organ dysfunction develops, especially in burn patients. Escharotomy may also dramatically reduce IAP in the case of abdominal burns.

Intra-abdominal hypertension and abdominal compartment syndrome in pancreatitis, paediatrics, and trauma.

Intra-abdominal hypertension (IAH) is an important contributor to early organ dysfunction among patients with trauma and sepsis. However, the impact of increased intra-abdominal pressure (IAP) among pediatric, pregnant, non-septic medical patients, and those with severe acute pancreatitis (SAP), obesity, and burns has been studied less extensively. The aim of this review is to outline the pathophysiologic implications and treatment options for IAH and abdominal compartment syndrome (ACS) for the above patient populations. We searched MEDLINE and PubMed to identify relevant studies. There is an increasing awareness of IAH in general medicine. The incidence of IAH and, to a lesser extent, ACS is high among patients with SAP. IAH should always be suspected and IAP measured routinely. In children, normal IAP in mechanically ventilated patients is approximately 7 ± 3 mm Hg. As an IAP of 10-15 mm Hg has been associated with organ damage in children, an IAP greater than 10 mm Hg should be considered IAH in these patients. Moreover, as ACS may occur in children at an IAP lower than 20 mm Hg, any elevation in IAP higher than 10 mm Hg associated with new organ dysfunction should be considered ACS in children until proven otherwise. Monitor IAP trends and be aware that specific interventions may need to be instituted at lower IAP than the current ACS definitions accommodate. Finally, IAH and ACS can occur both in abdominal trauma and extra-abdominal trauma patients. Early mechanical hemorrhage control and the avoidance of excessive fluid resuscitation are key elements in preventing IAH in trauma patients. IAH and ACS have been associated with many conditions beyond the general ICU patient. In adults and in children, the focus should be on the early recognition of IAH and the prevention of ACS. Patients at risk for IAH should be identified early during their treatment (with a low threshold to initiate IAP monitoring). Appropriate actions should be taken when IAP increases above 20 mm Hg, especially in patients developing difficulty with ventilation. Although on-operative measures should be instituted first, one should not hesitate to resort to surgical decompression if they fail.