Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10-15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils-the ability to form neutrophil extracellular traps (NETs)-may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.

https://rupress.org/jem/article-pdf/217/6/e20200652/1414639/jem_20200652.pdf

Targeting potential drivers of COVID-19: Neutrophil extracellular traps.

Surveys show that physicians continue to prescribe low-dose dopamine for acute renal dysfunction, even though neither evidence nor editorials and reviews support its use. This meta-analysis found t...

/pdf/meta-analysis-low-dose-dopamine-increases-urine-output-but-4spggl3c7i.pdf

Meta-Analysis: Low-Dose Dopamine Increases Urine Output but Does Not Prevent Renal Dysfunction or Death

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.

/pdf/endothelial-dysfunction-and-immunothrombosis-as-key-1wamvfu8r3.pdf

Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19.

For half a century, controlled hypotension has been used to reduce bleeding and the need for blood transfusions, and provide a satisfactory bloodless surgical field. It has been indicated in oromaxillofacial surgery (mandibular osteotomy, facial repair), endoscopic sinus or middle ear microsurgery, spinal surgery and other neurosurgery (aneurysm), major orthopaedic surgery (hip or knee replacement, spinal), prostatectomy, cardiovascular surgery and liver transplant surgery. Controlled hypotension is defined as a reduction of the systolic blood pressure to 80-90 mm Hg, a reduction of mean arterial pressure (MAP) to 50-65 mm Hg or a 30% reduction of baseline MAP. Pharmacological agents used for controlled hypotension include those agents that can be used successfully alone and those that are used adjunctively to limit dosage requirements and, therefore, the adverse effects of the other agents. Agents used successfully alone include inhalation anaesthetics, sodium nitroprusside, nitroglycerin, trimethaphan camsilate, alprostadil (prostaglandin E1), adenosine, remifentanil, and agents used in spinal anaesthesia. Agents that can be used alone or in combination include calcium channel antagonists (e.g. nicardipine), beta-adrenoceptor antagonists (beta-blockers) [e.g. propranolol, esmolol] and fenoldopam. Agents that are mainly used adjunctively include ACE inhibitors and clonidine. New agents and techniques have been recently evaluated for their ability to induce effective hypotension without impairing the perfusion of vital organs. This development has been aided by new knowledge on the physiology of peripheral microcirculatory regulation. Apart from the adverse effects of major hypotension on the perfusion of vital organs, potent hypotensive agents have their own adverse effects depending on their concentration, which can be reduced by adjuvant treatment. Care with use limits the major risks of these agents in controlled hypotension; risks that are generally less important than those of transfusion or alternatives to transfusion. New hypotensive drugs, such as fenoldopam, adenosine and alprostadil, are currently being evaluated; however, they have disadvantages and a high treatment cost that limits their development in this indication. New techniques of controlled hypotension subscribe to the use of the natural hypotensive effect of the anaesthetic drug with regard to the definition of the ideal hypotensive agent. It must be easy to administer, have a short onset time, an effect that disappears quickly when administration is discontinued, a rapid elimination without toxic metabolites, negligible effects on vital organs, and a predictable and dose-dependent effect. Inhalation agents (isoflurane, sevoflurane) provide the benefit of being hypnotic and hypotensive agents at clinical concentrations, and are used alone or in combination with adjuvant agents to limit tachycardia and rebound hypertension, for example, inhibitors of the autonomic nervous system (clonidine, beta-blockers) or ACE inhibitors. When they are used alone, inhalation anaesthetics require high concentrations for a significant reduction in bleeding that can lead to hepatic or renal injury. The greatest efficacy and ease-of-use to toxicity ratio is for techniques of anaesthesia that associate analgesia and hypotension at clinical concentrations without the need for potent hypotensive agents. The first and oldest technique is epidural anaesthesia, but depending on the surgery, it is not always appropriate. The most recent satisfactory technique is a combination treatment of remifentanil with either propofol or an inhalation agent (isoflurane, desflurane or sevoflurane) at clinical concentrations. In light of the current literature, and because of their safety and ease of use, these two techniques are preferred.

Controlled hypotension: a guide to drug choice.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jth.13235

Contact system revisited: an interface between inflammation, coagulation, and innate immunity.

Effect of Controlled Hypotension Combined with Hemodilution on Gastric Intramural pH

Various techniques have been described for blind bedside placement of a post-pyloric feeding tube. However, there is no universal method and the technique depends on the local institutional resources and expertise. The purpose of this study was to evaluate a simple new technique for the bedside placement of a post-pyloric feeding tube in an intensive care unit using palpation to confirm tube position. We studied 47 consecutive ventilated patients (mean body mass index 22.4 ± 4.2 kg/m(2)) requiring enteral tube feeding for nutritional support. We monitored the maximum intensity point of injected air 'bubbling' by palpation and estimated tube position. We monitored the movement of the maximum intensity point from the left upper quadrant to the right upper quadrant. If the maximum intensity point on the right upper quadrant diminished or weakened, we considered the tube had proceeded beyond the pylorus. By palpation, we could feel the bubbling of the injected air in all patients, but four patients were excluded because of failure to complete the protocol. The overall success rate including the four excluded cases was 85.1% (40/47) on the first attempt and 91.5% (43/47) when we included the second attempt. The median time for 40 successful tube placements on the first attempt was 10 (7 to 23) minutes. Our new palpation technique can successfully detect the position of a feeding tube in the stomach and help guide the tube to the correct location in the post-pyloric portion of the stomach in lean critically ill patients.

https://journals.sagepub.com/doi/pdf/10.1177/0310057X1204000119

A new technique for post-pyloric feeding tube placement by palpation in lean critically ill patients.

We performed prospective study to determine whether the increase of calories with preoperative oral intake will prevent ketosis due to preoperative starvation in children receiving afternoon surgery. Twenty five children (aged 3 to 9 years) for elective minor surgery under general anesthesia with sevoflurane and nitrous oxide were divided into morning surgery group and afternoon surgery group, and the latter was divided into 2 groups according to calories contained in the clear fluid. The calorie of the clear fluid in the afternoon group P was 0.24 kcal.ml-1, and that in the afternoon group A was 0.48 kcal.ml-1. The calorie of the clear fluid in the morning group was 0.48 kcal. ml-1. The levels of blood glucose, blood ketone body, plasma free fatty acids (NEFA), insulin, glucagon and cortisol were measured before and during intravenous infusion in three groups. The urinary catecholamine excretion was measured in the urine collected from 18:00 on the day before operation day until the start of anesthesia. There were no significant differences in the levels of blood glucose, NEFA, insulin, glucagon, cortisol and urinary catecholamine excretion. But the level of blood ketone body only in the afternoon group P was significantly higher than that in the morning group. But the levels of NEFA before infusion were higher than average in 40-60 percent of patients of each group. These data suggest that the increasing preoperative calories with oral intake will prevent ketosis due to preoperative starvation in the afternoon group as well as in the morning group. But the short duration of starvation only can not prevent lipolysis completely.

The effect of calories of preoperative oral intake on the glucose metabolic response in children

Effects of dopamine and dobutamine on renal function and urinary excretion of prostaglandin E2 (UPGE) were studied in 21 elderly patients who underwent abdominal surgery. Fractional sodium excretion (FeNa), creatinine clearance (Ccr), urinary volume (UV, ml.kg-1.min-1) and UPGE were measured on the first and second postoperative day. These patients were divided into three groups: i.e. C (control), DA (dopamine) and DB (dobutamine) groups. Group DA received dopamine 2 mcg.kg-1.min-1 beginning at six o'clock on the first postoperative day. Group DB received dobutamine 2 mcg.kg-1.min-1. There were no significant differences in UV and UPGE among these three groups. Ccr was significantly higher on the second postoperative day than that on the first postoperative day in DA group. FeNa in DA group was higher than in C group on the second postoperative day. The relationship between UPGE and UV was not determined. These results suggest that DA improve renal functions in the elderly.

Toshiaki Nakamura

Papers

Effect of Controlled Hypotension Combined with Hemodilution on Gastric Intramural pH

A new technique for post-pyloric feeding tube placement by palpation in lean critically ill patients.

The effect of calories of preoperative oral intake on the glucose metabolic response in children

Effects of dopamine and dobutamine on renal function and urinary excretion of prostaglandin E2 in elderly postoperative patients

Hemodynamic and catecholamine responses during rapid sequence induction with propofol in hypertensive patients