Table 1 Twenty recommendations to individualize interventions in the early resuscitation of patients with sepsis

1.

We recommend individualizing the timing of ICU admission. It should ideally be within minutes in severely ill patients but can be less urgent in less severe cases. No time limit is applicable for all patients. The decision may be influenced by the level of care available within ward areas and by ICU bed availability and, of course, by the physiological status and reserve of the patient

2.

We recommend individualizing the decision to admit to the ICU. Many patients develop sepsis at the end of their life. Patients with palliative care orders and treatment escalation plans that preclude advanced organ support should generally not be admitted

3.

We recommend individualizing the timing of antibiotic therapy. Administration should be prompt in the presence of septic shock but less urgent in less severe cases, enabling more time to perform investigations, confirm the diagnosis and likely source, and seek expert advice

4.

We recommend individualizing the need for and timing of tracheal intubation, based on careful clinical assessment, including level of consciousness, respiratory rate and work of breathing, hemodynamic status, and assessment of gas exchange. Delaying tracheal intubation may lead to respiratory and even cardiac arrest, with dire consequences, yet premature use of invasive mechanical ventilation can expose the patient to ventilator-induced lung injury, distant organ complications, and increased risk of nosocomial lung infection

5.

We recommend individualizing respiratory settings in mechanically ventilated patients, including driving pressure, tidal volume and level of positive end-expiratory pressure (PEEP), aiming at the lowest possible mechanical power. PEEP could be adjusted to lung recruitment capacity

6.

We recommend individualizing oxygenation targets, taking oxygen delivery into account. Exposure to high PaO₂ levels may be associated with worse outcomes, except perhaps in necrotizing infections. Extreme oxygenation values (too conservative or too liberal) should generally be avoided

7.

We recommend individualizing sedation therapies, recognizing that many septic patients need little or even no sedation. Tracheal intubation per se is not a sufficient indication for administration of sedative agents. Sedative agents reduce vascular tone and myocardial contractility, and may also alter immune function

8.

We recommend individualizing initial fluid resuscitation. No single formula can be applied to all patients, as fluid requirements vary substantially (depending on the source of sepsis and preexisting cardiovascular function). This is particularly true for the suggestion to give at least 30 mL/kg of fluid within the first 3 h. A young patient without comorbidities is more likely to tolerate administration of a large volume of fluid than a fragile elderly patient with severe cardiac or renal disease

9.

We recommend individualizing fluid therapy using dynamic challenges. Assessment of pulse pressure variation (PPV) or stroke volume variation (SVV) is possible only in deeply sedated mechanically ventilated patients with no spontaneous breathing. Alternative methods, including fluid challenges or passive leg raising, are therefore more widely applicable

10.

We recommend individualizing the type of intravenous fluid administered. For example, albumin administration may be considered in an edematous patient with profound hypoalbuminemia or prolonged non-response to crystalloids

11.

We recommend monitoring of chloride levels if saline solutions are administered. Saline solutions should not be banned, but one must keep in mind that liberal administration of saline results in hyperchloremia, and this may result in a worsening metabolic acidosis and renal impairment

12.

We recommend individualizing the initiation of vasopressor therapy. Fluid pre-loading may be considered in less severe cases, whereas fluid co-loading parallel to vasopressor initiation should be preferred in cases of life-threatening hypotension or a low diastolic arterial pressure

13.

We recommend individualizing arterial blood pressure levels. Although a mean value of 65 mmHg may be recommended as an initial goal, the optimal level may be higher in patients with a history of hypertension, atherosclerosis or chronic kidney disease. Conversely it may be lower in younger patients without previous vascular problems, in those with chronically low arterial pressure, or in whom adequate tissue perfusion is maintained

14.

We recommend optimizing oxygen delivery, based on clinical assessment complemented by careful hemodynamic assessment including measurement of mixed (or central) venous oxygen saturation (SvO₂) and even carbon dioxide-derived variables. A low SvO₂ in the presence of a normal SaO₂ indicates inadequate overall oxygen delivery to the tissues. More importantly, a normal or high SvO₂ does not exclude tissue hypoxia

15.

We recommend a multimodal approach to assessing tissue perfusion, including mental status, urine output, peripheral perfusion, and blood lactate levels, taking into consideration the physiological reserve of the patient

16.

We recommend individualizing blood transfusion. Transfusion should be based not only on measurements of hemoglobin concentration, but on clinical evaluation including persisting signs of tissue hypoperfusion, and measurements of SvO₂ and lactate

17.

We recommend individualizing administration of inotropic agents when tissue hypoperfusion relates to impaired cardiac function (documented at least by echocardiography). The choice and the dose of the inotropic agent should be based on individual hemodynamic monitoring with repeated measurements

18.

We recommend individualizing the decision to administer corticosteroids, not only for septic shock, but also for other conditions such as severe pneumonia and ARDS

19.

We recommend involving senior colleagues and consultants, especially since guidelines are most useful for non-experts. Team work, communication and multidisciplinary teams are essential aspects. One of the most overarching recommendations is to seek for guidance from other colleagues and to clearly document the rationale for an intervention –be it recommended or not in the guidelines

20.

We recommend carefully measuring and monitoring the effects of any therapeutic measures undertaken and deciding whether or not to continue or adjust treatment accordingly