Towards definitions of critical illness and critical care using concept analysis

Objective As critical illness and critical care lack consensus definitions, this study aims to explore how the concepts are used, describe their defining attributes and propose potential definitions. Design We used the Walker and Avant stepwise approach to concept analysis. The uses and definitions of the concepts were identified through a scoping review of the literature and an online survey of 114 global clinical experts. Through content analysis of the data we extracted codes, categories and themes to determine the concepts defining attributes and we proposed potential definitions. To assist understanding, we present model, related and contrary cases concerning the concepts, we identified antecedents and consequences to the concepts, and defined empirical referents. Results The defining attributes of critical illness were a high risk of imminent death; vital organ dysfunction; requirement for care to avoid death; and potential reversibility. The defining attributes of critical care were the identification, monitoring and treatment of critical illness; vital organ support; initial and sustained care; any care of critical illness; and specialized human and physical resources. Our proposed definition of critical illness is, a state of ill health with vital organ dysfunction, a high risk of imminent death if care is not provided and the potential for reversibility. Our proposed definition of critical care is, the identification, monitoring and treatment of patients with critical illness through the initial and sustained support of vital organ functions. Conclusion The concepts critical illness and critical care lack consensus definitions and have varied uses. Through concept analysis of uses and definitions in the literature and among experts we have identified the defining attributes of the concepts and propose definitions that could aid clinical practice, research, and policy making.

A Multifunctional, Low-Volume Resuscitation Cocktail Improves Vital Organ Blood Flow and Hemostasis in a Pig Model of Polytrauma with Traumatic Brain Injury

The resuscitation of polytrauma with hemorrhagic shock and traumatic brain injury (TBI) is a balance between permissive hypotension and maintaining vital organ perfusion. There is no current optimal solution. This study tested whether a multifunctional resuscitation cocktail supporting hemostasis and perfusion could mitigate blood loss while improving vital organ blood flow during prolonged limited resuscitation. Anesthetized Yorkshire swine were subjected to fluid percussion TBI, femur fracture, catheter hemorrhage, and aortic tear. Fluid resuscitation was started when lactate concentration reached 3–4 mmol/L. Animals were randomized to one of five groups. All groups received hydroxyethyl starch solution and vasopressin. Low- and high-dose fibrinogen (FBG) groups additionally received 100 and 200 mg/kg FBG, respectively. A third group received TXA and low-dose FBG. Two control groups received albumin, with one also including TXA. Animals were monitored for up to 6 h. Blood loss was decreased and vital organ blood flow was improved with low- and high-dose fibrinogen compared to albumin controls, but survival was not improved. There was no additional benefit of high- vs. low-dose FBG on blood loss or survival. TXA alone decreased blood loss but had no effect on survival, and combining TXA with FBG provided no additional benefit. Pooled analysis of all groups containing fibrinogen vs. albumin controls found improved survival, decreased blood loss, and improved vital organ blood flow with fibrinogen delivery. In conclusion, a low-volume resuscitation cocktail consisting of hydroxyethyl starch, vasopressin, and fibrinogen concentrate improved outcomes compare to controls during limited resuscitation of polytrauma.

Case Report: Hypercoagulopathy as a Severe Long-term Complication of Post SARS-CoV-19 Infection, Autopsy Findings in Three Patients

Background: It has been less than two years since the advent of the COVID-19 pandemic, and there are plenty of publications describing the clinical and pathological features of this severe infectious disease, damaging not only lung but also other vital organs. However, the pathologic findings of long-term complications post virus infection have rarely been described. Case presentation: We are reporting three autopsy cases from patients who had COVID-19 one to six months before death. The patients were all SARS-CoV-2 negative at admission but expired shortly. At autopsy, the first patient showed subacute diffuse myocardial ischemic injury with microthrombi in pericardial small vessels, whereas the second patient showed catastrophic acute and subacute pulmonary infarctions with hemothorax leading to respiratory failure. The third patient showed subacute severe cerebral infarcts in the left middle cerebral artery region. Conclusions: Our findings suggest the hypercoagulopathy and subsequent vital organ damage may persist beyond the active phase of SARS-CoV-2 infection. It is essential to evaluate and continue monitoring the COVID-19 patients after recovery, so as to identify the ones with vital organ injury in a timely manner and to take the steps to prevent severe consequence of COVID-19 complications.

The Protective Effect of a Novel Cross-Linked Hemoglobin-Based Oxygen Carrier on Hypoxia Injury of Acute Mountain Sickness in Rabbits and Goats

Hypoxia is the major cause of acute altitude hypoxia injury in acute mountain sickness (AMS). YQ23 is a kind of novel bovine-derived, cross-linked hemoglobin-based oxygen carrier (HBOC). It has an excellent capacity for carrying and releasing oxygen. Whether YQ23 has a protective effect on the acute altitude hypoxia injury in AMS is unclear. In investigating this mechanism, the hypobaric chamber rabbit model and plain-to-plateau goat model were used. Furthermore, this study measured the effects of YQ23 on the ability of general behavior, general vital signs, Electrocardiograph (ECG), hemodynamics, vital organ injury markers, and blood gases in hypobaric chamber rabbits and plain-to-plateau goats. Our results showed that the ability of general behavior (general behavioral scores, GBS) (GBS: 18 ± 0.0 vs. 14 ± 0.5, p < 0.01) and the general vital signs weakened [Heart rate (HR, beats/min): 253.5 ± 8.7 vs. 301.1 ± 19.8, p < 0.01; Respiratory rate (RR, breaths/min): 86.1 ± 5.2 vs. 101.2 ± 7.2, p < 0.01] after exposure to plateau environment. YQ23 treatment significantly improved the ability of general behavior (GBS: 15.8 ± 0.5 vs. 14.0 ± 0.5, p < 0.01) and general vital signs [HR (beats/min): 237.8 ± 24.6 vs. 301.1 ± 19.8, p < 0.01; RR (breaths/min): 86.9 ± 6.6 vs. 101.2 ± 7.2, p < 0.01]. The level of blood PaO2 (mmHg) (115.3 ± 4.7 vs. 64.2 ± 5.6, p < 0.01) and SaO2(%) (97.7 ± 0.7 vs. 65.8 ± 3.1, p < 0.01) sharply decreased after exposure to plateau, YQ23 treatment significantly improved the blood PaO2 (mmHg) (97.6 ± 3.7 vs. 64.2 ± 5.6, p < 0.01) and SaO2(%) (82.7 ± 5.2 vs. 65.8 ± 3.1, p < 0.01). The cardiac ischemia and injury marker was increased [troponin (TnT, μg/L):0.08 ± 0.01 vs. 0.12 ± 0.02, p < 0.01], as well as the renal [blood urea nitrogen (BUN, mmol/L): 6.0 ± 0.7 vs. 7.3 ± 0.5, p < 0.01] and liver injury marker [alanine aminotransferase (ALT, U/L): 45.8 ± 3.6 vs. 54.6 ± 4.2, p < 0.01] was increased after exposure to a plateau environment. YQ23 treatment markedly alleviated cardiac ischemia [TnT (μg/L):0.10 ± 0.01 vs 0.12 ± 0.02, p < 0.01] and mitigated the vital organ injury. Besides, YQ23 exhibited no adverse effects on hemodynamics, myocardial ischemia, and renal injury. In conclusion, YQ23 effectively alleviates acute altitude hypoxia injury of AMS without aside effects.

Double-Effect Donation Disputed

In “Double Effect Donation,” Camosy and Vukov argue that “there are circumstances in which it is morally permissible for a healthy individual to donate their organs even though their death is a foreseeable outcome”. They propose that a living donor could ethically donate an entire, singular, vital organ while knowing that this act would result in death. In reply, I argue that it is not ethical for a living person to donate an entire, singular, vital organ. Moreover, mutatis mutandis, it is not ethical for surgeons and others to perform such a deadly operation. For to do so is “intentionally to cause the death of the donor in disposing of his organs”. Such an act violates the dead donor rule which holds that an entire, singular, vital organ may be taken only from a corpse. Contrary to Camosy and Vukov’s claims, double-effect reasoning does not endorse such organ donation.

Hepatocytes and Its Role in Metabolism

Liver is one of the vital organ that performs many functions in the human body. Prominently it acts as a metabolizing organ for the body. This chapter elaborately describes hepatocytes along with their morphological features. In addition, it explains the structure of hepatocytes and different parts such as kupffer cells, hepatic stellate and hepatic sinusoids. Moreover present chapter elaborates the varieties of functions that hepatocytes perform such as filtration of blood, acting as a viral incubator, lipophagy and regulation of insulin and glucose. This chapter also explains hepatic injury that is caused by chronic consumption of alcohol along with the mechanism behind it.

The Use of CytoSorb Therapy in Critically Ill COVID-19 Patients: Review of the Rationale and Current Clinical Experiences

The COVID-19 pandemic has led to the biggest global health crisis of our lifetime. There is accumulating evidence that a substantial number of critically ill COVID-19 patients exhibit a dysregulated host response manifesting as cytokine storm or cytokine release syndrome, which in turn contributes to the high observed rates of mortality. Just as in other hyperinflammatory conditions, extracorporeal cytokine removal may have potential beneficial effects in this subgroup of COVID-19 patients. The CytoSorb blood purification device is the most extensively investigated cytokine removal platform with considerable evidence suggesting that early intervention can provide rapid hemodynamic stabilization and improvement in vital organ functions. The purpose of this review is to provide an overview of the pathophysiological background of hyperinflammation in COVID-19 and to summarize the currently available evidence on the effects of hemoadsorption in these patients.

A randomized phase 3 study of ixazomib–dexamethasone versus physician’s choice in relapsed or refractory AL amyloidosis

In the first phase 3 study in relapsed/refractory AL amyloidosis (TOURMALINE-AL1 NCT01659658), 168 patients with relapsed/refractory AL amyloidosis after 1–2 prior lines were randomized to ixazomib (4 mg, days 1, 8, 15) plus dexamethasone (20 mg, days 1, 8, 15, 22; n = 85) or physician’s choice (dexamethasone ± melphalan, cyclophosphamide, thalidomide, or lenalidomide; n = 83) in 28-day cycles until progression or toxicity. Primary endpoints were hematologic response rate and 2-year vital organ deterioration or mortality rate. Only the first primary endpoint was formally tested at this interim analysis. Best hematologic response rate was 53% with ixazomib–dexamethasone vs 51% with physician’s choice (p = 0.76). Complete response rate was 26 vs 18% (p = 0.22). Median time to vital organ deterioration or mortality was 34.8 vs 26.1 months (hazard ratio 0.53; 95% CI, 0.32–0.87; p = 0.01). Median treatment duration was 11.7 vs 5.0 months. Adverse events of clinical importance included diarrhea (34 vs 30%), rash (33 vs 20%), cardiac arrhythmias (26 vs 15%), nausea (24 vs 14%). Despite not meeting the first primary endpoint, all time-to-event data favored ixazomib–dexamethasone. These results are clinically relevant to this relapsed/refractory patient population with no approved treatment options.