As with the first SIBICC effort that produced a management algorithm for adult sTBI patients with ICP monitoring alone , this work uses Delphi process-based mechanics to provide basic evidence guiding integration of individual treatment modalities into management algorithms for patients with combined ICP/PbtO2 monitoring. The process amalgamated the practice-based recommendations of 42 international, experienced, clinically active neurotrauma practitioners from those disciplines involved in acute post-traumatic (ICU) care by means of consensus achieved with blinded voting. Such formalized integration of expert opinion provides the most basic level of evidence towards organizing and standardizing care, relevant to all neurotrauma practitioners but particularly to centers not specifically expert in the management of sTBI or those considering initiating combined ICP/PbtO2 monitoring.
Given the class III status of this evidence, these algorithms should be considered as a suggested treatment method without proven superiority over other applicable methods. They represent a safe and modern approach to sTBI care. They are not a standard of care nor are they likely to represent the best treatment approach in a given instance. They are not legally binding and they are not designed as quality assurance monitoring tools. They do not represent the approach of any individual CWG member and should not be substituted for thoughtful clinical judgment. Variability within individual patients or patient cohorts (e.g. center variations) may necessitate local adaptation, which is entirely within the nature of this offering.
The combination of ICP and PbtO2 monitoring lends itself to several possible protocol structures. One option is to conceptualize ICP and PbtO2 management separately and to present them as distinct pathways, as has been done for the paediatric sTBI guidelines [4, 5]. The other is to maintain integration of the two monitors and create separate algorithms for the three pathologic combinations of ICP and PbtO2 status. Our panel felt that when high ICP and low PbtO2 are present concurrently ideal management would not simply reflect a simple combination of care provided when high ICP and low PbtO2 each exist in isolation. In particular, the CWG felt that mechanical ventilation requires distinct management when both high ICP and low PbtO2 are present concurrently. In the interest of supporting precision medicine and to ease clinical application by providing specific, separate protocols for individual pathological combinations, we chose to present three distinct algorithms (Figs. 2,3,4,5). For a given combination (type B, C, or D), the relevant protocol should be applied. Changes in clinical status should prompt adjustment to the newly germane algorithm as well as a thoughtful clinical approach.
Conditions of tiered treatment
The use of tiers attempts to balance the benefits and efficacy of an agent against risks inherent to its use. General clinical management is considered tier zero. Treatment of intracranial hypertension or brain hypoxia will generally begin at tier one. Movement to higher tiers reflects increasingly aggressive interventions. Here, treatments in any given tier are considered equivalent, with the selection of one treatment over another based on individual patient characteristics and physician discretion. During any given episode being addressed, multiple items from a single tier can be trialed individually or in combination with the goal of a rapid response. The provider should maintain awareness of the duration of any episode and consider moving to more aggressive interventions in a higher tier quickly if the patient is not responding. In some cases, it might be preferable to skip one or more tiers (e.g. choosing to decompress a patient with midline shift due to hemispheric swelling and very high initial ICP). No individual agent or combination thereof is critical to success in managing TBI. Clinical judgment must always determine the final management strategy.
Tier‐zero (Fig. 1) recommendations apply to sTBI patients who are admitted to an ICU in whom the decision to concurrently monitor ICP and PbtO2 has been made. Management recommendations for sTBI patients without ICP monitoring are published elsewhere . The goal of tier‐zero is to establish a stable, neuroprotective physiologic baseline regardless of eventual ICP or PbtO2 readings. Tier-zero sedatives and analgesics target comfort and ventilator tolerance rather than ICP or PbtO2. Temperature management targets the avoidance of fever (defined by the CWG as core temperature > 38 °C). Consistent with the BTF Guidelines , the minimal cerebral perfusion pressure (CPP) threshold is 60 mm Hg.
The algorithm for type B patients differs from that recommended for the management of intracranial hypertension in patients with ICP-monitoring alone  due to available PbtO2 evidence that cerebral hypoxia is not present. Although tiers one and two are the same as for the ICP-only algorithm, this difference is reflected in the recommendation that hyperventilation to a PaCO2 of 30–32 mmHg/4.0–4.3 kPa can be considered in tier three. The CWG does not recommend either hypertonic saline or mannitol as preferable and uses the same limits for serum sodium and osmolality for both agents. They recommend CSF drainage if an external ventricular drain is available and consideration of placing one if other means are used to monitor ICP. They also recommend considering the possibility of seizures as the etiology of intracranial hypertension in tier one.
The CWG recommends consideration of a trial of neuromuscular blockade (with continuation if it is effective) as a tier two intervention. They also support mild hyperventilation (PaCO2 32–35 mm Hg/4.7 kPa) at this level. The CWG also recommends the consideration of autoregulation testing via CPP manipulation to determine whether CPP augmentation might be applicable. The MAP challenge is performed under stable conditions to prevent confounding (e.g., no other active changes in care should be made during the challenge, including adjustments in sedation, analgesia, EVD drainage or other physiological parameters). To perform the challenge :
Record baseline monitor parameters at the beginning of the challenge (e.g., ICP, MAP and CPP).
Initiate or titrate a vasopressor to increase the MAP by 10 mm Hg for up to 20 min.
Observe the interaction between the MAP, ICP, CPP and PbtO2 during the challenge.
Record monitor parameters at the end of the challenge.
Evaluate the observed responses and recorded values for evidence of sPAR status. Disrupted sPAR will present as a sustained increase in ICP with MAP elevation.
Adjust the target MAP back to baseline (disrupted sPAR) or to the chosen new, elevated target (intact sPAR).
As noted above, tier three treatment in type B parallels that for ICP-monitor-only sTBI patients, with the exception that moderate hyperventilation (PaCO2 30–32 mmHg/4.0–4.3 kPa) is also included.
Type C treatments include interventions known to directly or indirectly improve PbtO2 values, largely based upon the collective experience of the expert CWG. A great deal of discussion surrounded augmentation of oxygenation in terms of benefit versus toxicity and the possibility that higher monitor readings may not parallel improved oxygen availability when FiO2 or PaO2 are pushed very high. FiO2 can effectively increase PbtO2 values. Although the CWG approved upward FiO2 adjustment to 60% at tier one, further oxygenation manipulation was left to the discretion of the physician in terms of manipulation of ventilator dynamics, PEEP, FiO2, etc. Therefore, at tier two, elevating the PaO2 up to 150 mm Hg is recommended but the means is meant to be fine-tuned to the patient. Further elevation of the PaO2 was controversial but the final decision was to recommend normobaric hyperoxia above 150 mm Hg at tier three.
The notion of blood transfusion to ameliorate low PbtO2 values also generated significant discussion. Harm from the transfusion of blood products is increasingly recognized [8, 9] and many on the panel felt that transfusion had little impact on PbtO2 values in their experience. The CWG finally settled on limiting blood transfusion to tier three, recommending consideration of transfusing one unit of PRBCs in the setting of a PbtO2 < 20 mm Hg and an Hgb < 9 g/L. It was acknowledged that blood transfusion would be a stronger consideration in patients with active organ ischemia (eg. cardiac ischemia).
Other recommendations in type C differ from those in type B patients. First-tier recommendations include setting the target CPP at the upper limit of the generally accepted range of 60–70 mm Hg as blood pressure augmentation can be an effective strategy for increasing PbtO2. The avoidance of hypocarbia is also stressed in tier one; hypercarbia induces vasodilation which can improve PbtO2 though this strategy increases intracranial blood volume and risks ICP elevation. At tier two, the CWG supported consideration of setting an ICP threshold below the general target of 22 mm Hg (acknowledging that this group does not have intracranial hypertension by definition). They also allowed compliance manipulation via CSF drainage.
Type D recommendations combine ICP and PbtO2 treatments, but aim to limit those treatments that would exacerbate either pathology. At tier one, therefore, although the CWG supported elevation of the FiO2 to 60% and setting the CPP threshold to the upper limit of the normal range (i.e., 70 mm Hg), they recommended against hyperventilation to any degree which could worsen PbtO2. In tier two, the CWG recommended raising the PaO2 to as high as 150 mm Hg in addition to considering neuromuscular blockade and CPP manipulation based on autoregulation testing but did not support lowering the ICP threshold. At tier three, they combined ICP-based recommendations for pentobarbital/thiopentone coma or decompressive craniectomy with PbtO2-based treatments including normobaric hyperoxia to above 150 mm Hg and limited transfusion. Notably, decompressive craniectomy can enable more aggressive PbtO2 augmentation strategies such as hypercarbia which can exacerbate ICP; it can also mitigate the intracranial hypertension associated with MAP augmentation in patients who are not autoregulating.
The CWG carried forward those items that they did not recommend for treating intracranial hypertension in ICP-Only patients (Table 1). They added three PbtO2-specific items to this list. They recommended against using high-dose barbiturates or cooling specifically for the management of PbtO2 though these therapies can be thoughtfully administered for other indications. They also recommended against routinely using hypercarbia (PaCO2 > 45 mm Hg/6.0 kPa in type D patients given the risk of elevating ICP.
Stepping to a higher tier is a potential indicator of increased disease severity. As higher tiers represent interventions with increased associated risks, the CWG recommends reassessing the patient’s basic intra-and extra-cranial physiologic status and reconsidering the surgical status of intracranial mass lesions (e.g. contusions) not previously considered operative. If the patient is at a non‐specialist center at the point of upward tier advancement, the CWG recommended considering consultation with and potential transfer to a TBI center with increased resources if possible within the regional healthcare environment. When desired, transfer is best completed before clinical decline precludes it.
Critical Neuroworsening represents a specific situation of critical deterioration requiring emergent evaluation and management. ‘Neuroworsening’ was first defined as a potential intermediate-outcome variable for TBI trials , it was adapted for the BEST:TRIP trial  and subsequent management studies for limited resource environments . The CWG modified the criteria, terming the new criteria ‘Critical Neuroworsening’ and added it to promote its recognition as a critical event and guide expeditious evaluation and consideration of empiric therapy.