Case report: Successful experience using continuous infusion of meropenem in a geriatric patient with hip fracture complicated by sepsis

This article highlights a clinical case of successful treatment of a 79-year-old multimorbid patient with a hip fracture resulting from a household injury. On the first day, the patient’s injury was complicated by infection and pneumonia. As a result, arterial hypotension, tachysystole, and respiratory failure progressed. With manifestations of sepsis, the patient was transferred to the intensive care unit. Surgical treatment in such a situation was contraindicated due to the high operational and anesthesiological risks, the unstable severe condition of the patient, as well as the presence of concomitant pathology in the form of coronary heart disease, obesity, and schizophrenia. According to the new sepsis management guideline, it was decided to use a continuous 24-h infusion of meropenem in addition to the complex treatment of sepsis. The use of continuous infusion of meropenem in this clinical situation may have caused the patient’s clinical improvement, which increased her quality of life and decreased the length of ICU stay and total hospital stay, despite an unfavorable cumulative prognosis and a high risk of in-hospital mortality

Critical care bed capacity in Asian countries and regions

Objective: To assess the number of adult critical care beds in Asian countries and regions in relation to population size. Design: Cross-sectional observational study. Setting: Twenty-three Asian countries and regions, covering 92.1% of the continent’s population. Participants: Ten low-income and lower-middle–income economies, five upper-middle–income economies, and eight high-income economies according to the World Bank classification. Interventions: Data closest to 2017 on critical care beds, including ICU and intermediate care unit beds, were obtained through multiple means, including government sources, national critical care societies, colleges, or registries, personal contacts, and extrapolation of data. Measurements and Main Results: Cumulatively, there were 3.6 critical care beds per 100,000 population. The median number of critical care beds per 100,000 population per country and region was significantly lower in low- and lower-middle–income economies (2.3; interquartile range, 1.4–2.7) than in upper-middle–income economies (4.6; interquartile range, 3.5–15.9) and high-income economies (12.3; interquartile range, 8.1–20.8) (p = 0.001), with a large variation even across countries and regions of the same World Bank income classification. This number was independently predicted by the World Bank income classification on multivariable analysis, and significantly correlated with the number of acute hospital beds per 100,000 population (r2 = 0.19; p = 0.047), the universal health coverage service coverage index (r2 = 0.35; p = 0.003), and the Human Development Index (r2 = 0.40; p = 0.001) on univariable analysis. Conclusions: Critical care bed capacity varies widely across Asia and is significantly lower in low- and lower-middle–income than in upper-middle–income and high-income countries and regions

The COVID-19 vaccination acceptance/hesitancy rate and its determinants among healthcare workers of 91 Countries: A multicenter cross-sectional study.

The aim of this study was to investigate the COVID-19 vaccination acceptance rate and its determinants among healthcare workers in a multicenter study. This was a cross-sectional multi-center survey conducted from February 5 to April 29, 2021. The questionnaire consisted of 26 items in 6 subscales. The English version of the questionnaire was translated into seven languages and distributed through Google Forms using snowball sampling; a colleague in each country was responsible for the forward and backward translation, and also the distribution of the questionnaire. A forward stepwise logistic regression was utilized to explore the variables and questionnaire factors tied to the intention to COVID-19 vaccination. 4630 participants from 91 countries completed the questionnaire. According to the United Nations Development Program 2020, 43.6 % of participants were from low Human Development Index (HDI) regions, 48.3 % high and very high, and 8.1 % from medium. The overall vaccination hesitancy rate was 37 %. Three out of six factors of the questionnaire were significantly related to intention to the vaccination. While 'Perceived benefits of the COVID-19 vaccination' (OR: 3.82, p-value<0.001) and 'Prosocial norms' (OR: 5.18, p-value<0.001) were associated with vaccination acceptance, 'The vaccine safety/cost concerns' with OR: 3.52, p-value<0.001 was tied to vaccination hesitancy. Medical doctors and pharmacists were more willing to take the vaccine in comparison to others. Importantly, HDI with OR: 12.28, 95 % CI: 6.10-24.72 was a strong positive determinant of COVID-19 vaccination acceptance. This study highlighted the vaccination hesitancy rate of 37 % in our sample among HCWs. Increasing awareness regarding vaccination benefits, confronting the misinformation, and strengthening the prosocial norms would be the primary domains for maximizing the vaccination coverage. The study also showed that the HDI is strongly associated with the vaccination acceptance/hesitancy, in a way that those living in low HDI contexts are more hesitant to receive the vaccine

Prognostic evaluation of quick sequential organ failure assessment score in ICU patients with sepsis across different income settings

Background There is conflicting evidence on association between quick sequential organ failure assessment (qSOFA) and sepsis mortality in ICU patients. The primary aim of this study was to determine the association between qSOFA and 28-day mortality in ICU patients admitted for sepsis. Association of qSOFA with early (3-day), medium (28-day), late (90-day) mortality was assessed in low and lower middle income (LLMIC), upper middle income (UMIC) and high income (HIC) countries/regions. Methods This was a secondary analysis of the MOSAICS II study, an international prospective observational study on sepsis epidemiology in Asian ICUs. Associations between qSOFA at ICU admission and mortality were separately assessed in LLMIC, UMIC and HIC countries/regions. Modified Poisson regression was used to determine the adjusted relative risk (RR) of qSOFA score on mortality at 28 days with adjustments for confounders identified in the MOSAICS II study. Results Among the MOSAICS II study cohort of 4980 patients, 4826 patients from 343 ICUs and 22 countries were included in this secondary analysis. Higher qSOFA was associated with increasing 28-day mortality, but this was only observed in LLMIC (p < 0.001) and UMIC (p < 0.001) and not HIC (p = 0.220) countries/regions. Similarly, higher 90-day mortality was associated with increased qSOFA in LLMIC (p < 0.001) and UMIC (p < 0.001) only. In contrast, higher 3-day mortality with increasing qSOFA score was observed across all income countries/regions (p < 0.001). Multivariate analysis showed that qSOFA remained associated with 28-day mortality (adjusted RR 1.09 (1.00–1.18), p = 0.038) even after adjustments for covariates including APACHE II, SOFA, income country/region and administration of antibiotics within 3 h. Conclusions qSOFA was independently associated with 28-day mortality in ICU patients admitted for sepsis. In LLMIC and UMIC countries/regions, qSOFA was associated with early to late mortality but only early mortality in HIC countries/regions

The story of critical care in Asia: a narrative review

Background Asia has more critically ill people than any other part of our planet. The aim of this article is to review the development of critical care as a specialty, critical care societies and education and research, the epidemiology of critical illness as well as epidemics and pandemics, accessibility and cost and quality of critical care, culture and end-of-life care, and future directions for critical care in Asia. Main body Although the first Asian intensive care units (ICUs) surfaced in the 1960s and the 1970s and specialisation started in the 1990s, multiple challenges still exist, including the lack of intensivists, critical care nurses, and respiratory therapists in many countries. This is aggravated by the brain drain of skilled ICU staff to high-income countries. Critical care societies have been integral to the development of the discipline and have increasingly contributed to critical care education, although critical care research is only just starting to take off through collaboration across groups. Sepsis, increasingly aggravated by multidrug resistance, contributes to a significant burden of critical illness, while epidemics and pandemics continue to haunt the continent intermittently. In particular, the coronavirus disease 2019 (COVID-19) has highlighted the central role of critical care in pandemic response. Accessibility to critical care is affected by lack of ICU beds and high costs, and quality of critical care is affected by limited capability for investigations and treatment in low- and middle-income countries. Meanwhile, there are clear cultural differences across countries, with considerable variations in end-of-life care. Demand for critical care will rise across the continent due to ageing populations and rising comorbidity burdens. Even as countries respond by increasing critical care capacity, the critical care community must continue to focus on training for ICU healthcare workers, processes anchored on evidence-based medicine, technology guided by feasibility and impact, research applicable to Asian and local settings, and rallying of governments for support for the specialty. Conclusions Critical care in Asia has progressed through the years, but multiple challenges remain. These challenges should be addressed through a collaborative approach across disciplines, ICUs, hospitals, societies, governments, and countries

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis

Importance: Meropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, setting, and participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main outcomes and measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial registration: ClinicalTrials.gov Identifier: NCT03452839

Usage of Meropenem Continuous Infusion for Treatment of Infectious Complications in Orthopedic Elderly Patients with Anemia: A Case Series

Background and Objectives: The prolonged infusion of meropenem is recommended by guidelines for the treatment of sepsis. However, studies provide controversial data on the advantages of prolonged infusions over intermittent ones. In our opinion, this can be related to age, which possibly distorts the final data, as older people have age-related characteristics. In our study, we analyzed the ventilatory status, laboratory tests and vital signs of the patient and carried out microbiological cultures. Materials and Methods: This was a prospective single-center case series investigation conducted from June 2022 to June 2023. The objective of this study was to evaluate the effectiveness of continuous infusion in elderly patients with severe infectious complications after orthopedic interventions. The primary endpoints were 28-day survival and the emergence of new multidrug-resistant strains. Secondary endpoints were long-term mortality and length of stay in the ICU. Results: Three patients (median age 65, 100% female) received a continuous infusion of meropenem. Two patients were alive at hospital discharge, and one patient died on the 105th day of hospitalization. Multi-resistant bacteria were observed in one patient. Conclusions: The use of a continuous meropenem infusion in the complex treatment of purulent-septic complications in elderly patients with periprosthetic infection and anemia probably led to clinical improvement in these case reports. However, the emergence of new pan-resistant strains and overall mortality using this infusion technique remains unclear. Further, high-quality RCTs for the elderly are needed

Effects of morphine or ketamine in rats with asphyxial cardiac arrest: a pilot study

Acute hypoxia results in uncontrolled release of glutamate and the consequent stimulation of N-methyl-D-aspartate (NMDA) receptors, which affects the whole ionic homeostasis and finally activates apoptosis of neurons. A potential therapeutic approach to prevent this sequence of events is a blockade of NMDA receptors. Meanwhile, in different models of acute hypoxia, activation of delta-opioid receptors demonstrates significant cardioand neuroprotective effects with a consequent increase in animal survival. Thus, we aimed to test the effects of Morphine or Ketamine on hemodynamics, acid-base status and early survival in rats after asphyxia cardiac arrest (ACA)

The influences of morphine or ketamine pre-treatment on hemodynamic, acid-base status, biochemical markers of brain damage and early survival in rats after asphyxial cardiac arrest

Background In different models of hypoxia, blockade of opioid or N-methyl-D-aspartate (NMDA) receptors shows cardio- and neuroprotective effects with a consequent increase in animal survival. The aim of the study was to investigate effects of pre-treatment with Morphine or Ketamine on hemodynamic, acid-base status, early survival, and biochemical markers of brain damage in a rat model of asphyxial cardiac arrest (ACA). Methods Under anaesthesia with Thiopental Sodium 60 mg/kg, i.p., Wistar rats (n = 42) were tracheostomized and catheters were inserted in a femoral vein and artery. After randomization, the rats were pre-treated with: Morphine 5 mg/kg i.v. (n = 14); Ketamine 40 mg/kg i.v. (n = 14); or equal volume of i.v. NaCl 0.9% as a Control (n = 14). ACA was induced by corking of the tracheal tube for 8 min, and defined as a mean arterial pressure (MAP) < 20 mmHg. Resuscitation was started at 5 min after cardiac arrest (CA). Invasive MAP was recorded during experiments. Arterial pH and blood gases were sampled at baseline (BL) and 10 min after CA. At the end of experiments, all surviving rats were euthanised, brain and blood samples for measurement of Neuron Specific Enolase (NSE), s100 calcium binding protein B (s100B) and Caspase-3 (CS-3) were retrieved. Results At BL no differences between groups were found in hemodynamic or acid-base status. After 3 min of asphyxia, all animals had cardiac arrest (CA). Return of spontaneous circulation (MAP > 60 mmHg) was achieved in all animals within 3 min after CA. At the end of the experiment, the Ketamine pre-treated group had increased survival (13 of 14; 93%) compared to the Control (7 of 14; 50%) and Morphine (10 of 14; 72%) groups (p = 0.035). Biochemical analysis of plasma concentration of NSE and s100B as well as an analysis of CS-3 levels in the brain tissue did not reveal any differences between the study groups. Conclusion In rats after ACA, pre-treatment with Morphine or Ketamine did not have any significant influence on hemodynamic and biochemical markers of brain damage. However, significantly better pH level and increased early survival were found in the Ketamine pre-treated group

Clinical validation of a new “call-out algorithm” for postoperative pain management: a two-center prospective randomized trial

The goal of modern postoperative pain management is to relieve pain while keeping side effects to a minimum. Still, in recent investigations, between 20% and 40% of all postoperative patients report high levels of pain after surgery, while 20-30% experience adverse effects of opioid analgetics [1,2]. In a study, in which the hospitals had introduced pain management guided by the patients' own numerical scale scores, the investigators unexpectedly found that the side effects of drugs had more than doubled [3]. The authors suggested that more than just a one-dimensional numerical assessment of pain should be undertaken, for the postoperative treatment to be safe and effective [3]. Recently, Efficacy Safety Score (ESS), a new "call-out algorithm" for monitoring of efficacy and safety of postoperative pain management and its side effects, was developed and implemented in clinical practice at Kongsberg hospital in Norway [4]. ESS was established after obtaining consensus between 10 international experts in a DELPHI process on which parameters that should be included in the score [4]. ESS consists of the sum of two subjective scores (Verbal Numeric Rate Scale of pain (VNRS) at rest and during mobilization) and four vital scores (consciousness level, postoperative nausea and vomiting, circulation and respiration status) [4]. In the present trial, we aimed to validate the influence of ESS registration and the application of a "call-out algorithm" on hospital length of stay (LOS) in two university hospitals of Kazakhstan and Russian Federation in which a policy of routine registration of pain as "the fifth vital sign" had not been adopted yet. Thus, the primary endpoint for the study was to assess LOS in groups of patients with different types of clinical data registration, while secondary endpoints were to compare the degree of mobilization, number of postoperative nonsurgical complications, and 28 days survival between the groups