10
important in patients with hypoxemic respiratory failure. Remark 1: Crystalloids include normal saline and Ringer’s lactate. Remark 2: Determine need for additional fluid boluses (250–500 mL in adults or 10–20 mL/kg in children) based on clinical response and improvement of perfusion targets. Perfusion targets include MAP (> 65 mmHg or age-appropriate targets in children), urine output (> 0.5 mL/kg/hr in adults, 1 mL/kg/hr in children), and improvement of skin mottling and extremity perfusion, capillary refill, heart rate, level of consciousness, and lactate. Remark 3: Consider dynamic indices of volume responsiveness to guide volume administration beyond initial resuscitation based on local resources and experience (5). These indices include passive leg raises, fluid challenges with serial stroke volume measurements, or variations in systolic pressure, pulse pressure, inferior vena cava size, or stroke volume in response to changes in intrathoracic pressure during mechanical ventilation. Remark 4: In pregnant women, compression of the inferior vena cava can cause a decrease in venous return and cardiac preload and may result in hypotension. For this reason, pregnant women with sepsis and or septic shock may need to be placed in the lateral decubitus position to off-load the inferior vena cava (58). Remark 5: Clinical trials conducted in resource-limited studies comparing aggressive versus conservative fluid regimens suggest higher mortality in patients treated with aggressive fluid regimens (56, 57). Do not use hypotonic crystalloids, starches, or gelatins for resuscitation. Remark 1: Starches are associated with an increased risk of death and acute kidney injury compared with crystalloids. The effects of gelatins are less clear, but they are more expensive than crystalloids (5, 59). Hypotonic (vs isotonic) solutions are less effective at increasing intravascular volume. Surviving Sepsis also suggests albumin for resuscitation when patients require substantial amounts of crystalloids, but this conditional recommendation is based on low-quality evidence (5). In adults, administer vasopressors when shock persists during or after fluid resuscitation. The initial blood pressure target is MAP ≥ 65 mmHg in adults and improvement of markers of perfusion. In children administer vasopressors if: 1. Signs of shock such as altered mental state; bradycardia or tachycardia (HR < 90 bpm or > 160 bpm in infants and H R < 70 bpm or > 150 bpm in children); prolonged capillary refill (> 2 seconds) or feeble pulses; tachypnea; mottled or cool skin or petechial or purpuric rash; increased lactate; oliguria persists after two repeat boluses; or 2. age-appropriate blood pressure targets are not achieved; or 3. signs of fluid overload are apparent (6). 10 Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: Interim guidance If central venous catheters are not available, vasopressors can be given through a peripheral IV, but use a large vein and closely monitor for signs of extravasation and local tissue necrosis. If extravasation occurs, stop infusion. Vasopressors can also be administered through intraosseous needles. If signs of poor perfusion and cardiac dysfunction persist despite achieving MAP target with fluids and vasopressors, consider an inotrope such as dobutamine. Remark 1: Vasopressors (i.e. norepinephrine, epinephrine, vasopressin, and dopamine) are most safely given through a central venous catheter at a strictly controlled rate, but it is also possible to safely administer them via peripheral vein (60) and intraosseous needle. Monitor blood pressure frequently and titrate the vasopressor to the minimum dose necessary to maintain perfusion and prevent side effects. A recent study suggests that in adults 65 years or older a MAP 60–65 mmHg target is equivalent to ≥ 65 mmHg (61). Remark 2: Norepinephrine is considered first-line treatment in adult patients; epinephrine or vasopressin can be added to achieve the MAP target. Because of the risk of tachyarrhythmia, reserve dopamine for selected patients with low risk of tachyarrhythmia or those with bradycardia. Remark 3: In children, epinephrine is considered first-line treatment, while norepinephrine can be added if shock persists despite optimal dose of epinephrine. Remark 4: No RCTs have compared dobutamine with placebo for clinical outcomes. Remark 5: See section 11 on adjunctive therapies for remarks on corticosteroids and sepsis. 10. Adjunctive therapies for COVID-19: corticosteroids Do not routinely give systemic corticosteroids for treatment of viral pneumonia outside clinical trials. Remark 1: A systematic review of observational studies of corticosteroids administered to patients with SARS reported no survival benefit and possible harms (avascular necrosis, psychosis, diabetes, and delayed viral clearance) (62). A systematic review of observational studies in influenza found a higher risk of mortality and secondary infections with corticosteroids; the evidence was judged as very low to low quality owing to confounding by indication (63). A subsequent study that addressed this limitation by adjusting for time-varying confounders found no effect on mortality (64). Finally, a recent study of patients receiving corticosteroids for MERS used a similar statistical approach and found no effect of corticosteroids on mortality but delayed LRT