Critical illness results in millions of deaths each year. Care for those with critical illness is often neglected due to a lack of prioritisation, co-ordination, and coverage of timely identification ...and basic life-saving treatments. To improve care, we propose a new focus on essential emergency and critical care (EECC)-care that all critically ill patients should receive in all hospitals in the world. Essential emergency and critical care should be part of universal health coverage, is appropriate for all countries in the world, and is intended for patients irrespective of age, gender, underlying diagnosis, medical specialty, or location in the hospital. Essential emergency and critical care is pragmatic and low-cost and has the potential to improve care and substantially reduce preventable mortality.
Critical illness is common throughout the world and has been the focus of a dramatic increase in attention during the COVID-19 pandemic. Severely deranged vital signs such as hypoxia, hypotension and ...low conscious level can identify critical illness. These vital signs are simple to check and treatments that aim to correct derangements are established, basic and low-cost. The aim of the study was to estimate the unmet need of such essential treatments for severely deranged vital signs in all adults admitted to hospitals in Malawi. We conducted a point prevalence cross-sectional study of adult hospitalized patients in Malawi. All in-patients aged greater than or equal to18 on single days Queen Elizabeth Central Hospital (QECH) and Chiradzulu District Hospital (CDH) were screened. Patients with hypoxia (oxygen saturation <90%), hypotension (systolic blood pressure <90mmHg) and reduced conscious level (Glasgow Coma Scale <9) were included in the study. The a-priori defined essential treatments were oxygen therapy for hypoxia, intravenous fluid for hypotension and an action to protect the airway for reduced consciousness (placing the patient in the lateral position, insertion of an oro-pharyngeal airway or endo-tracheal tube or manual airway protection). Of the 1135 hospital in-patients screened, 45 (4.0%) had hypoxia, 103 (9.1%) had hypotension, and 17 (1.5%) had a reduced conscious level. Of those with hypoxia, 40 were not receiving oxygen (88.9%). Of those with hypotension, 94 were not receiving intravenous fluids (91.3%). Of those with a reduced conscious level, nine were not receiving an action to protect the airway (53.0%). There was a large unmet need of essential treatments for critical illness in two hospitals in Malawi.
Acute respiratory distress syndrome (ARDS) is a life-threatening lung disease. It may occur during the pancytopenia phase following allogeneic hematopoietic cell transplantation (HCT). ARDS is rare ...following HCT. Mesenchymal stromal cells (MSCs) have strong anti-inflammatory effect and first home to the lung following intravenous infusion. MSCs are safe to infuse and have almost no side effects. During the Covid-19 pandemic many patients died from ARDS. Subsequently MSCs were evaluated as a therapy for Covid-19 induced ARDS. We report three patients, who were treated with MSCs for ARDS following HCT. Two were treated with MSCs derived from the bone marrow (BM). The third patient was treated with MSCs obtained from the placenta, so-called decidua stromal cells (DSCs). In the first patient, the pulmonary infiltrates cleared after infusion of BM-MSCs, but he died from multiorgan failure. The second patient treated with BM-MSCs died of aspergillus infection. The patient treated with DSCs had a dramatic response and survived. He is alive after 7 years with a Karnofsky score of 100%. We also reviewed experimental and clinical studies using MSCs or DSCs for ARDS. Several positive reports are using MSCs for sepsis and ARDS in experimental animals. In man, two prospective randomized placebo-controlled studies used adipose and BM-MSCs, respectively. No difference in outcome was seen compared to placebo. Some pilot studies used MSCs for Covid-19 ARDS. Positive results were achieved using umbilical cord and DSCs however, optimal source of MSCs remains to be elucidated using randomized trials.
Oxygen is a low-cost and life-saving therapy for patients with COVID-19. Yet, it is a limited resource in many hospitals in low income countries and in the 2020 pandemic even hospitals in richer ...countries reported oxygen shortages. An accurate understanding of oxygen requirements is needed for capacity planning. The World Health Organization estimates the average flow-rate of oxygen to severe COVID-19-patients to be 10 l/min. However, there is a lack of empirical data about the oxygen provision to patients. This study aimed to estimate the oxygen provision to COVID-19 patients with severe disease in a Swedish district hospital. A retrospective, medical records-based cohort study was conducted in March to May 2020 in a Swedish district hospital. All adult patients with severe COVID-19 -those who received oxygen in the ward and had no ICU-admission during their hospital stay-were included. Data were collected on the oxygen flow-rates provided to the patients throughout their hospital stay, and summary measures of oxygen provision calculated. One-hundred and twenty-six patients were included, median age was 70 years and 43% were female. On admission, 27% had a peripheral oxygen saturation of ≤91% and 54% had a respiratory rate of ≥25/min. The mean oxygen flow-rate to patients while receiving oxygen therapy was 3.0 l/min (SD 2.9) and the mean total volume of oxygen provided per patient admission was 16,000 l (SD 23,000). In conclusion, the provision of oxygen to severely ill COVID-19-patients was lower than previously estimated. Further research is required before global estimates are adjusted.
Immune system suppression during critical care contributes to the risk of acquired bacterial infections with Pseudomonas (P.) aeruginosa. Repeated exposure to endotoxin can attenuate systemic ...inflammatory cytokine responses. Mechanical ventilation affects the systemic inflammatory response to various stimuli.
To study the effect of pre-exposure to mechanical ventilation with and without endotoxin-induced systemic inflammation on P. aeruginosa growth and wet-to-dry weight measurements on lung tissue and plasma and bronchoalveolar lavage levels of tumor necrosis factor alpha, interleukins 6 and 10.
Two groups of pigs were exposed to mechanical ventilation for 24 hours before bacterial inoculation and six h of experimental pneumonia (total experimental time 30 h): A30h+Etx (n = 6, endotoxin 0.063 μg x kg-1 x h-1) and B30h (n = 6, saline). A third group, C6h (n = 8), started the experiment at the bacterial inoculation unexposed to endotoxin or mechanical ventilation (total experimental time 6 h). Bacterial inoculation was performed by tracheal instillation of 1x1011 colony-forming units of P. aeruginosa. Bacterial cultures and wet-to-dry weight ratio analyses were done on lung tissue samples postmortem. Separate group comparisons were done between A30h+Etx vs.B30h (Inflammation) and B30h vs. C6h (Ventilation Time) during the bacterial phase of 6 h.
P. aeruginosa growth was highest in A30h+Etx, and lowest in C6h (Inflammation and Ventilation Time both p<0.05). Lung wet-to-dry weight ratios were highest in A30h+Etx and lowest in B30h (Inflammation p<0.01, Ventilation Time p<0.05). C6h had the highest TNF-α levels in plasma (Ventilation Time p<0.01). No differences in bronchoalveolar lavage variables between the groups were observed.
Mechanical ventilation and systemic inflammation before the onset of pneumonia increase the growth of P. aeruginosa in lung tissue. The attenuated growth of P. aeruginosa in the non-pre-exposed animals (C6h) was associated with a higher systemic TNF-α production elicited from the bacterial challenge.
Global Critical Care is attracting increasing attention. At several million deaths per year, the worldwide burden of critical illness is greater than generally appreciated. Low income countries ...(LICs) have a disproportionally greater share of critical illness, and yet critical care facilities are scarce in such settings. Routines utilizing abnormal vital signs to identify critical illness and trigger medical interventions have become common in high-income countries but have not been investigated in LICs. The aim of the study was to assess whether the introduction of a vital signs directed therapy protocol improved acute care and reduced mortality in an Intensive Care Unit (ICU) in Tanzania.
Prospective, before-and-after interventional study in the ICU of a university hospital in Tanzania. A context-appropriate protocol that defined danger levels of severely abnormal vital signs and stipulated acute treatment responses was implemented in a four week period using sensitisation, training, job aids, supervision and feedback. Acute treatment of danger signs at admission and during care in the ICU and in-hospital mortality were compared pre and post-implementation using regression models. Danger signs from 447 patients were included: 269 pre-implementation and 178 post-implementation. Acute treatment of danger signs was higher post-implementation (at admission: 72.9% vs 23.1%, p<0.001; in ICU: 16.6% vs 2.9%, p<0.001). A danger sign was five times more likely to be treated post-implementation (Prevalence Ratio (PR) 4.9 (2.9-8.3)). Intravenous fluids were given in response to 35.0% of hypotensive episodes post-implementation, as compared to 4.1% pre-implementation (PR 6.4 (2.5-16.2)). In patients admitted with hypotension, mortality was lower post-implementation (69.2% vs 92.3% p = 0.02) giving a numbers-needed-to-treat of 4.3. Overall in-hospital mortality rates were unchanged (49.4% vs 49.8%, p = 0.94).
The introduction of a vital signs directed therapy protocol improved the acute treatment of abnormal vital signs in an ICU in a low-income country. Mortality rates were reduced for patients with hypotension at admission but not for all patients.
Endotoxin, a component of the outer membrane of Gram-negative bacteria, has been extensively studied as a stimulator of the innate immune response. However, the temporal aspects and exposure-response ...relationship of endotoxin and resulting cytokine induction and tolerance development is less well defined. The aim of this work was to establish an in silico model that simultaneously captures and connects the in vivo time-courses of endotoxin, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and associated tolerance development. Data from six studies of porcine endotoxemia in anesthetized piglets (n = 116) were combined and used in the analysis, with purified endotoxin (Escherichia coli O111:B4) being infused intravenously for 1-30 h in rates of 0.063-16.0 μg/kg/h across studies. All data were modelled simultaneously by means of importance sampling in the non-linear mixed effects modelling software NONMEM. The infused endotoxin followed one-compartment disposition and non-linear elimination, and stimulated the production of TNF-α to describe the rapid increase in plasma concentration. Tolerance development, observed as declining TNF-α concentration with continued infusion of endotoxin, was also driven by endotoxin as a concentration-dependent increase in the potency parameter related to TNF-α production (EC50). Production of IL-6 was stimulated by both endotoxin and TNF-α, and four consecutive transit compartments described delayed increase in plasma IL-6. A model which simultaneously account for the time-courses of endotoxin and two immune response markers, the cytokines TNF-α and IL-6, as well as the development of endotoxin tolerance, was successfully established. This model-based approach is unique in its description of the time-courses and their interrelation and may be applied within research on immune response to bacterial endotoxin, or in pre-clinical pharmaceutical research when dealing with study design or translational aspects.
Surgery and anesthesia have been linked to postoperative cognitive disturbance and increased risk of Alzheimer's disease. It is not clear by which mechanisms this increased risk for cognitive disease ...is mediated. Further, amyloid β production has been suggested to depend on the sleep-wake cycle and neuronal activity. The aim of the present study was to examine if cerebrospinal fluid (CSF) concentrations of a number of biomarkers for Alzheimer's disease-related processes, including amyloid β, neuronal injury, and inflammation, changed over time during intravenous anesthesia in surgical patients.
We included patients scheduled for hysterectomy via laparotomy during general anesthesia with intravenous propofol and remifentanil. CSF samples were obtained before, during, and after surgery (5 h after induction) and tested for 27 biomarkers. Changes over time were tested with linear mixed effects models.
A total of 22 patients, all females, were included. The mean age was 50 years (± 9 SD). The mean duration of the anesthesia was 145 min (± 40 SD). Interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, and vascular endothelial growth factor A increased over time. IL-15 and IL-7 decreased slightly over time. Macrophage inflammatory protein 1β and placental growth factor also changed significantly. There were no significant effects on amyloid β (Aβ) or tau biomarkers.
Surgery and general anesthesia with intravenous propofol and remifentanil induce, during and in the short term after the procedure, a neuroinflammatory response which is dominated by monocyte attractants, without biomarker signs of the effects on Alzheimer's disease pathology or neuronal injury.
Protective ventilation with lower tidal volumes reduces systemic and organ-specific inflammation. In sepsis-induced encephalopathy or acute brain injury the use of protective ventilation has not been ...widely investigated (experimentally or clinically). We hypothesized that protective ventilation would attenuate cerebral inflammation in a porcine endotoxemic sepsis model. The aim of the study was to study the effect of tidal volume on cerebral inflammatory response, cerebral metabolism and brain injury. Nine animals received protective mechanical ventilation with a tidal volume of 6 mL × kg
and nine animals were ventilated with a tidal volume of 10 mL × kg
. During a 6-h experiment, the pigs received an endotoxin intravenous infusion of 0.25 µg × kg
× h
. Systemic, superior sagittal sinus and jugular vein blood samples were analysed for inflammatory cytokines and S100B. Intracranial pressure, brain tissue oxygenation and brain microdialysis were sampled every hour.
No differences in systemic or sagittal sinus levels of TNF-α or IL-6 were seen between the groups. The low tidal volume group had increased cerebral blood flow (p < 0.001) and cerebral oxygen delivery (p < 0.001), lower cerebral vascular resistance (p < 0.05), higher cerebral metabolic rate (p < 0.05) along with higher cerebral glucose consumption (p < 0.05) and lactate production (p < 0.05). Moreover, low tidal volume ventilation increased the levels of glutamate (p < 0.01), glycerol (p < 0.05) and showed a trend towards higher lactate to pyruvate ratio (p = 0.08) in cerebral microdialysate as well as higher levels of S-100B (p < 0.05) in jugular venous plasma compared with medium-high tidal volume ventilation.
Contrary to the hypothesis, protective ventilation did not affect inflammatory cytokines. The low tidal volume group had increased cerebral blood flow, cerebral oxygen delivery and cerebral metabolism together with increased levels of markers of brain injury compared with medium-high tidal volume ventilation.
Background Patients with critical illness have a high risk of mortality. Key decision-making in the health system affecting the outcomes of critically ill patients requires epidemiological evidence, ...but the burden of critical illness is largely unknown. This study aimed to estimate the prevalence of critical illness in a Swedish region. Secondary objectives were to estimate the proportion of hospital inpatients who are critically ill and to describe the in-hospital location of critically ill patients. Methods A prospective, multi-center, population-based, point-prevalence study on specific days in 2017-2018. All adult (> 18 years) in-patients, regardless of admitting specially, in all acute hospitals in Sörmland, and the patients from Sörmland who had been referred to university hospitals, were included. Patients in the operating theatres, with a psychiatric cause of admission, women in active labor and moribund patients, were excluded. All participants were examined by trained data collectors. Critical illness was defined as "a state of ill health with vital organ dysfunction, a high risk of imminent death if care is not provided and a potential for reversibility". The presence of one or more severely deranged vital signs was used to classify critical illness. The prevalence of critical illness was calculated as the number of critically ill patients divided by the number of adults in the region. Results A total of 1269 patients were included in the study. Median age was 74 years and 50% of patients were female. Critical illness was present in 133 patients, resulting in an adult population prevalence of critical illness per 100,000 people of 19.4 (95% CI 16.4-23.0). The proportion of patients in hospital who were critically ill was 10.5% (95% CI 8.8-12.3%). Among the critically ill, 125 95% CI 94.0% (88.4-97.0%) were cared for in general wards. Conclusions The prevalence of critical illness was higher than previous, indirect estimates. One in ten hospitalized patients were critically ill, the large majority of which were cared for in general wards. This suggests a hidden burden of critical illness of potential public health, health system and hospital management significance.
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