Stress Hyperglycemia in Critically Ill Patients: Insight Into Possible Molecular Pathways

Severe sepsis, systemic inflammatory response syndrome (SIRS), and traumatic brain injury are frequently associated with hyperglycemia in non-diabetic patients. In patients suffering from any of these conditions, hyperglycemia at admission to an intensive care unit (ICU) is directly correlated with increased mortality or morbidity. Although there was initial enthusiasm for insulin treatment to blood glucose levels below 110 mg/dL in these patients, recent understanding suggests that the potential for hypoglycemic complications make this approach potentially dangerous. More moderate glucose control seems to be more beneficial than the aggressive glucose lowering initially suggested. An important publication has shown that hyperlactatemia accompanying hyperglycemia could be the real culprit in bad outcomes. This suggests that coupling moderate glucose lowering with therapeutic agents which might treat the underlying metabolic disturbances in these conditions may be a better strategy. The key metabolic disturbance in these three conditions seems to be persistent glycolysis as an energy source even in the presence of adequate tissue oxygenation (the Warburg Effect). We look at recent advances in understanding aerobic glycolysis and possibly the action of DPP4 on incretins resulting in insulin dysregulation and suggest key metabolic pathways involved in hyperglycemia regulation

Relationship of tissue dimensions and three captive bolt placements on cadaver heads from mature swine (Sus scrofa domesticus) > 200 kg body weight

Three penetrating captive bolt (PCB) placements were tested on cadaver heads from swine with estimated body weight (BW) >200 kg (sows = 232.9 ± 4.1 kg; boars = 229.3 ± 2.6 kg). The objectives were to determine tissue depth, cross-sectional brain area, visible brain damage (BD), regions of BD, and bolt-brain contact; and determine relationships between external head dimensions and tissue depth at each placement. A Jarvis PAS – Type P 0.25R PCB with a Long Stunning Rod Nosepiece Assembly and 3.5 gr power loads was used at the following placements on heads from 111 sows and 46 boars after storage at 2-4° C for approximately 62 h before treatment: FRONTAL (F) – 3.5 cm superior to the optic orbits at midline, TEMPORAL (T) – at the depression posterior to the lateral canthus of the eye within the plane between the lateral canthus and the base of the ear, or BEHIND EAR (BE) – directly caudal to the pinna of the ear on the same plane as the eyes and targeting the middle of the opposite eye. For sows, the bolt path was in the plane of the brain for 42/42 (100%, 95% CI: 91.6-100.0%) F heads, 39/40 (97.5%, 95% CI: 86.8-99.9%) T heads, and 34/39 (87.5%, 95% CI: 72.6-95.7%) BE heads; for the heads that could reliably be assessed for BD damage was detected in 25/26 (96.2%, 95% CI: 80.4-99.9%) F heads, 24/35 (68.6%, 95% CI: 50.7-83.2%) T heads, and 5/40 (12.5%, 95% CI: 4.2-26.8%) BE heads. For boars, the bolt path was in the plane of the brain for 17/17 (100.0%, 95% CI: 80.5-100.0%) F heads, 18/18 (100.0%, 95% CI: 81.5-100.0%) T heads, and 14/14 (100.0%, 95% CI: 76.8-100.0%) BE heads; damage was detected in 11/12 (91.7%, 95% CI: 61.5-99.8%) F heads, 2/15 (13.3%, 95% CI: 1.7-40.5%) T heads, and 7/14 (50.0%, 95% CI: 23.0-77.0%) BE heads. Tissue depth was reported as mean ± standard error followed by 95% one-sided upper reference limit (URL). For sows, total tissue thickness was different (P 200 kg BW, F placement may be more effective than T or BE due to less soft tissue thickness, which may reduce concussive force. The brain was within the plane of bolt travel for 100% of F heads with brain damage for 96.2% and 91.7% of F sow and boar heads, respectively.This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Animal Science following peer review. The version of record: Anderson, Karly N., Kaysie J. Allen, Angela Baysinger, Madonna Benjamin, Jennifer Berger, James R. Claus, Brian J. Greco et al. "Relationship of tissue dimensions and three captive bolt placements on cadaver heads from mature swine (Sus scrofa domesticus)> 200 kg body weight." 99, no. 12 Journal of Animal Science (2021) is available online at DOI: 10.1093/jas/skab327. Copyright The Author(s) 2021. Posted with permission

Patients with Risk Factors for Complications Do Not Require Longer Antimicrobial Therapy for Complicated Intra-Abdominal Infection

A prospective, multicenter, randomized controlled trial found that four days of antibiotics for source-controlled complicated intra-abdominal infection resulted in similar outcomes when compared with a longer duration. We hypothesized that patients with specific risk factors for complications also had similar outcomes. Short-course patients with obesity, diabetes, or Acute Physiology and Chronic Health Evaluation II ≥15 from the STOP-IT trial were compared with longer duration patients. Outcomes included incidence of and days to infectious complications, mortality, and length of stay. Obese and diabetic patients had similar incidences of and days to surgical site infection, recurrent intra-abdominal infection, extra-abdominal infection, and Clostridium difficile infection. Short- and long-course patients had similar incidences of complications among patients with Acute Physiology and Chronic Health Evaluation II ≥15. However, there were fewer days to the diagnosis of surgical site infection (9.5 ± 3.4 vs 21.6 ± 6.2, P = 0.010) and extra-abdominal infection (12.4 ± 6.9 vs 21.8 ± 6.1, P = 0.029) in the short-course group. Mortality and length of stay was similar for all groups. A short course of antibiotics in complicated intraabdominal infection with source control seems to have similar outcomes to a longer course in patients with diabetes, obesity, or increased severity of illness

Patients with Complicated Intra-Abdominal Infection Presenting with Sepsis Do Not Require Longer Duration of Antimicrobial Therapy

A recent prospective, multicenter, randomized controlled trial found that 4 days of antibiotics after source control of complicated intra-abdominal infections resulted in similar outcomes when compared with longer duration. We hypothesized that the subset of patients presenting with sepsis have similar outcomes when treated with the shorter course of antibiotics. Patients from the STOP-IT (Study to Optimize Peritoneal Infection Therapy) trial database meeting criteria for sepsis (ie, temperature 38°C and a WBC count 12,000 cells/mm(3)) were analyzed. Patients had been randomized to receive antibiotics until 2 days after the resolution of fever, leukocytosis, and ileus, with a maximum of 10 calendar days of therapy (n = 45), or to receive a fixed short-course of antibiotics for 4 ± 1 calendar days (n = 67). Outcomes included incidence of and time to surgical site infection, recurrent intra-abdominal infection, Clostridium difficile infection, and extra-abdominal infections, as well as hospital days and mortality. One hundred and twelve of the 588 patients in the STOP-IT database met criteria for sepsis and were adherent to the protocol. With regard to short- vs long-course therapy, surgical site infection (11.9% vs 8.9%; p = 0.759), recurrent intra-abdominal infection (11.9% vs 13.3%; p = 1.00), extra-abdominal infection (11.9% vs 8.9%; p = 0.759), hospital days (7.4 ± 5.5 days vs 9.0 ± 7.5 days; p = 0.188), days to recurrent intra-abdominal infection (12.5 ± 6.6 days vs 18.0 ± 8.1 days; p = 0.185), days to extra-abdominal infection (12.6 ± 5.8 days vs 17.3 ± 3.9 days; p = 0.194), and mortality (1.5% vs 0%; p = 1.00) were similar. There were no cases of C difficile infection. Days to surgical site infection (6.9 ± 3.5 days vs 21.3 ± 6.1 days; p < 0.001) were fewer in the 4-day therapy group. There was no difference in outcomes between short and long-course antimicrobial therapy in patients with complicated intra-abdominal infection presenting with sepsis. Our findings suggest that the presence of systemic illness does not mandate a longer antimicrobial course if source control of complicated intra-abdominal infection is obtained