Risk factors and interventions associated with mortality or survival in adult COVID-19 patients admitted to critical care: a systematic review and meta-analysis

Patients with confirmed COVID-19 admitted to intensive care units have a high mortality rate, which appears to be associated with increasing age, male sex, smoking history, hypertension and diabetes mellitus. Methods: A systematic review to determine risk factors and interventions associated with mortality/survival in adult patients admitted to an intensive care unit (ICU) with confirmed COVID-19/SARS-CoV-2 infection. The protocol was registered with PROSPERO (CRD42020181185).Results: The search identified 483 abstracts between 1 January and 7 April 2020, of which nine studies were included in the final review. Only one study was of low bias. Advanced age (odds ratio [OR] 11.99, 95% confidence interval [CI] 5.35­18.62) and a history of hypertension were associated with mortality (OR 4.17, 95% CI 2.90­5.99). Sex was not associated with mortality. There was insufficient data to assess the association between other comorbidities, laboratory results or critical care risk indices and mortality.The critical care interventions of mechanical ventilation (OR 6.25, 95% CI 0.75­51.93), prone positioning during ventilation (OR 2.06, 95% CI 0.20­21.72), and extracorporeal membrane oxygenation (ECMO) (OR 8.00, 95% CI 0.69, 92.33) were not associated with mortality. The sample size was insufficient to conclusively determine the association between these interventions and ICUmortality. The need for inotropes or vasopressors was associated with mortality (OR 6.36, 95% CI 1.89­21.36). Conclusion: The studies provided little granular data to inform risk stratification or prognostication of patients requiring intensive

Autonomic control of cardiorespiratory interactions in fish, amphibians and reptiles

Control of the heart rate and cardiorespiratory interactions (CRI) is predominantly parasympathetic in all jawed vertebrates, with the sympathetic nervous system having some influence in tetrapods. Respiratory sinus arrhythmia (RSA) has been described as a solely mammalian phenomenon but respiration-related beat-to-beat control of the heart has been described in fish and reptiles. Though they are both important, the relative roles of feed-forward central control and peripheral reflexes in generating CRI vary between groups of fishes and probably between other vertebrates. CRI may relate to two locations for the vagal preganglionic neurons (VPN) and in particular cardiac VPN in the brainstem. This has been described in representatives from all vertebrate groups, though the proportion in each location is variable. Air-breathing fishes, amphibians and reptiles breathe discontinuously and the onset of a bout of breathing is characteristically accompanied by an immediate increase in heart rate plus, in the latter two groups, a left-right shunting of blood through the pulmonary circuit. Both the increase in heart rate and opening of a sphincter on the pulmonary artery are due to withdrawal of vagal tone. An increase in heart rate following a meal in snakes is related to withdrawal of vagal tone plus a non-adrenergic-non-cholinergic effect that may be due to humoral factors released by the gut. Histamine is one candidate for this role.

Control of respiration in fish, amphibians and reptiles

Fish and amphibians utilise a suction/force pump to ventilate gills or lungs, with the respiratory muscles innervated by cranial nerves, while reptiles have a thoracic, aspiratory pump innervated by spinal nerves. However, fish can recruit a hypobranchial pump for active jaw occlusion during hypoxia, using feeding muscles innervated by anterior spinal nerves. This same pump is used to ventilate the air-breathing organ in air-breathing fishes. Some reptiles retain a buccal force pump for use during hypoxia or exercise. All vertebrates have respiratory rhythm generators (RRG) located in the brainstem. In cyclostomes and possibly jawed fishes, this may comprise elements of the trigeminal nucleus, though in the latter group RRG neurons have been located in the reticular formation. In air-breathing fishes and amphibians, there may be separate RRG for gill and lung ventilation. There is some evidence for multiple RRG in reptiles. Both amphibians and reptiles show episodic breathing patterns that may be centrally generated, though they do respond to changes in oxygen supply. Fish and larval amphibians have chemoreceptors sensitive to oxygen partial pressure located on the gills. Hypoxia induces increased ventilation and a reflex bradycardia and may trigger aquatic surface respiration or air-breathing, though these latter activities also respond to behavioural cues. Adult amphibians and reptiles have peripheral chemoreceptors located on the carotid arteries and central chemoreceptors sensitive to blood carbon dioxide levels. Lung perfusion may be regulated by cardiac shunting and lung ventilation stimulates lung stretch receptors.