Optimal Blood Pressure Targets in Different Shock States

By Arnaldo Lopez-Ruiz, MD, and Miguel Quintana, MD, FACC

Dr. Lopez-Ruiz is Attending Physician, Department of Critical Care Medicine, AdventHealth Orlando, FL.
Dr. Quintana is Director, Institute Cardiovascular, Migone Hospital, Asunción, Paraguay.

Management of blood pressure (BP) in different shock states is a repetitive question needing definite answers for the intensive care physician. Striking a balance between hypoperfusion-induced hypotension and increasing doses of vasopressors is always a challenge. In general, limited literature exists from mainly observational retrospective studies, which may be subject to bias.

In the recent past, randomized controlled trials (RCTs) and larger databases have contributed more data on certain types of shock. Most of the literature regarding BP targets is in septic shock patients; in other forms of shock, BP targets often are extrapolated from patients with septic shock. This review will discuss the different shock states and the suggested BP targets for the different subsets of patients.

Septic Shock

In a recent, large retrospective analysis of a registry database across 110 intensive care units (ICUs), hypotension as a time-weighted average was associated with a higher risk of myocardial injury (MI), acute kidney injury (AKI), and death in septic patients.¹ On closer analysis, risks of MI and AKI are lower when the mean arterial pressure (MAP) is maintained > 85 mmHg. However, this does not imply that consistent elevation of MAP > 85 mmHg in all septic patients will result in lower rates of AKI and MI due to the lack of good-quality RCTs evaluating this question.

In addition to the drawbacks of registry-based or cohort-based data, where controlling for different variables can be challenging, studies done with surrogate physiological parameters as endpoints for resuscitation in septic patients also do not answer the question of BP target decisively.² In a randomized, multicenter trial by Asfar et al, there was no significant difference in outcomes for septic patients comparing a MAP of
65 mmHg to 70 mmHg vs. 80 mmHg to 85 mmHg.³ However, a subgroup analysis of patients with chronic hypertension showed a lower incidence of AKI or need for renal replacement therapy (RRT) in the high BP group (80 mmHg to 85 mmHg). A multicenter French study by Lamontagne et al also found no difference between the high and low BP groups except that a subset of elderly patients (age > 75 years) who were targeted for a higher BP had statistically significant greater mortality.⁴ The same author performed the study 65-Trial, in which patients older than 65 years of age with vasodilatory shock were randomized to either a permissive hypotension group with a MAP goal of 60 mmHg to 65 mmHg or usual care with vasopressors titrated at the discretion of the treating provider. Patients in the permissive hypotension group had overall lower exposure to vasopressors in terms of median duration and total dose. There was no difference in the primary outcome of 90-day mortality between groups. In contrast to SEPSISPAM,³ patients with chronic hypertension in the permissive hypotension group did not have significantly higher rates of RRT.⁵

In a pooled patient meta-analysis of higher vs. lower BP targets, higher BP targets were no better than lower BP targets in septic shock. In fact, among those patients who were enrolled after receiving vasopressor supports for > 6 hours, patients assigned to the higher BP group seemed to have a higher mortality (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.33-6.74) as compared to patients assigned to the lower BP group. This also was true for specific subgroups of patients, such as those with chronic hypertension and congestive cardiac failure.⁶

Multiple studies and meta-analyses have shown no difference in mortality when comparing noradrenaline to vasopressin (or its analog terlipressin) in septic shock.^7,8 Initiation of vasopressor support with vasopressin or its analogs terlipressin or selepressin resulted in a higher incidence of digital and bowel ischemia vs. a higher risk of atrial fibrillation (AF) with the initiation of noradrenaline as the first vasopressor.^8,9

With regard to patients with sepsis and advanced cirrhosis who develop AKI due to hepatorenal syndrome-AKI, observational studies suggest that the use of terlipressin or norepinephrine with a target MAP of 70 mmHg to 75 mmHg or 10 mmHg to 20 mmHg above baseline is associated with renal recovery, lower progression to severe AKI, and need for RRT.^10,11

In summary, a review of the literature supports a MAP of > 65 mmHg as an acceptable target in patients with septic shock. Patients with chronic hypertension and age < 75 years could be considered for a greater target (> 75 mmHg to 85 mmHg) to decrease the risk of developing AKI. However, this may not be applicable for elderly patients > 75 years of age given the risk of arrhythmias and stroke. Further RCTs currently are being conducted, which could give better answers for patients with septic shock in the future.

Hemorrhagic/Hypovolemic Shock

The concept of fluid resuscitation in a patient with hemorrhagic shock dates back more than 40 years. In these cases of shock, hemorrhage may not have occurred to a marked degree because the BP is too low and the blood flow too weak to overcome the resistance due to arterial vasoconstriction and by the blood clot.¹² Attempts to normalize BP in the presence of an active hemorrhage can create a vicious cycle of more bleeding with the normalized pressure, resulting in the need for more transfusions and/or fluids. This cycle needs to be interrupted until the etiology of the hemorrhage is actively controlled. Therefore, field trauma literature encourages restrictive crystalloid administration and permissive hypotension (systolic blood pressure [SBP] goal: 90 mmHg) in patients actively bleeding until control of the hemorrhage is achieved. This concept generally is applied to patients before their arrival to a trauma center with general surgery and massive transfusion capabilities.

This concept of permissive hypotension is based in animal studies. Specifically, in a swine model of uncontrolled hemorrhage due to aortic injury, resumption of active bleeding (> 0.5 cc/minute) and rupture of the immature new clot formed was observed when the mean arterial BP reached 64 ± 2 mmHg.¹² A meta-analysis of nine animal studies, which investigated permissive hypotension and limited resuscitation after hemorrhage, reported a decrease in mortality with a relative risk of 0.37 (95% CI, 0.33-0.71) in favor of animals undergoing hypotensive fluid resuscitation compared to those undergoing normotensive resuscitation.¹³

There are very few studies evaluating this concept in human patients. In a study by Bickell et al, there was improved survival in patients presenting to the emergency department with penetrating trauma and systolic BP less than 90 mmHg who were randomized to delayed resuscitation (resuscitation fluids given at the time of operative intervention) compared to those patients assigned to immediate resuscitation (70% vs. 62%, respectively).¹⁴ Although this trial did not evaluate a specific target BP, patients assigned to the delayed intervention remained significantly more hypotensive than the immediate resuscitation group until operative resolution of the penetrating trauma (mean systolic BP 72 mmHg vs. 79 mmHg, respectively).

Furthermore, another RCT that enrolled patients in shock due to penetrating abdominal or thoracic injury found no differences in outcomes between patients with a higher target systolic BP of 100 mmHg vs. patients who received resuscitation fluids only if systolic BP was lower than 70 mmHg.¹⁵ In another analysis of 24,000 patients in the Los Angeles County Trauma Database with moderate to severe injury resulting in hemorrhagic complications with no head injuries, Edwards at al defined hypotension based on the different age ranges and then correlated with mortality.¹⁶ They reported optimal definitions of hypotension as systolic BP less than 100 mmHg for patients 20-49 years of age, less than 120 mmHg for patients 50-69 years of age, and less than 140 mmHg for patients 70 years of age and older. The optimal systolic BP for improved mortality in hemorrhagic shock increased significantly with increasing age. Therefore, current guidelines and diverse trauma societies recommend delayed resuscitation protocols and permissive hypotension with a target of systolic BP 50 mmHg to 70 mmHg and MAP > 50 mmHg in most patients with hemorrhagic shock due to trauma.^17-19 A special consideration is the elderly (> 70 years of age) trauma patient without major head injury who should be considered hypotensive with a systolic BP less than 140 mmHg. The current recommendations for patients with non-traumatic hemorrhagic shock (gastrointestinal, pulmonary, or urogenital bleeding) also reinforce achieving a systolic BP of 90 mmHg with a target hemoglobin level of 7 g/dL for most patients by using massive transfusion protocol and following the ratio 1:1:1 for red blood cells:plasma:platelet transfusions.¹⁷

It generally is not advised to use vasopressors (e.g., dopamine, epinephrine, or norepinephrine) for treatment of hemorrhagic shock. However, recent studies have shown promising benefits of using vasopressin as an adjunct to a massive transfusion protocol of blood products and prompt surgery to stop the hemorrhage. The lower association with arrhythmias and the potential for endogenous vasopressin deficiency in patients with hemorrhagic shock potentially contribute to the beneficial effect of vasopressin.^20,21 It also is associated with a reduction in the number of units of red blood cells transfused for patients with hemorrhagic shock.²²

Neurogenic Shock

Neurogenic shock is classically characterized by hypotension, hypothermia, and bradycardia and occurs in up to 90% of patients experiencing complete cervical spinal cord injury (SCI) with lesions above the level of T6, compared to a 50% incidence in patients with incomplete SCI. The mechanism by which SCI triggers hypotension is through sympathetic denervation due to interruption of the anterior interomedial tract resulting in arteriolar dilatation and relative hypovolemia (venous pooling), as well as unopposed parasympathetic drive resulting in bradycardia and decreased inotropism. This systemic hypotension can further impair perfusion to the spinal cord.²³ Optimal BP management in patients with SCI is largely inferred from data on cerebral autoregulation and perfusion goals for treatment of severe traumatic brain injury (TBI). Class II and III evidence suggests hemodynamic augmentation in SCI with a goal of maintaining MAP > 80 mmHg to 85 mmHg for at least seven days. This approach has been associated with improved neurological outcomes (i.e., less disability) in SCI patients.²⁴ Many controversies exist about the benefits of this strategy of inducing hypertension in the setting of acute SCI; detrimental effects of vasopressors should be weighed against the negative effects of spinal cord ischemia. A more practical approach would be titration of vasopressors based on spinal perfusion pressure (SPP) and cerebral spinal fluid pressure (CSFP), considering that SPP = MAP – CSFP. An SPP greater than 50 mmHg has been shown to maintain optimal spine perfusion.²³

Another subset of neurologic patients that requires close BP monitoring are those with TBI. In patients with severe TBI, hypotension and hypoxia were independent risk factors for increased mortality and were strong predictors for poor neurological outcome. An analysis of 700 older patients with severe TBI from the Traumatic Coma Data Bank reported a 150% increase in mortality in those patients with hypotension.²⁵ Cerebral perfusion pressure is a surrogate for the adequacy of cerebral blood flow (CBF); therefore, intracranial cerebral pressure (ICP) and MAP should be monitored closely in patients with severe TBI. Current management guidelines for severe TBI advocate for a cerebral perfusion pressure (CPP) threshold of 60 mmHg to 70 mmHg (CPP = MAP – ICP). Driving CPP above 70 mmHg with the use of vasopressors and/or intravascular volume expansion has been associated with significantly higher rates of respiratory distress and prolonged mechanical ventilation. Thus, aggressive management of CPP to a target greater than 70 mmHg is not recommended. Overall, hypotension should be avoided, with a goal systolic BP of 100 mmHg to 110 mmHg or greater. Intravascular resuscitation with isotonic crystalloids should be the initial step in therapy. In cases of refractory low CPPs, vasopressors may be considered.²³

Cardiogenic Shock

In general, BP targets in cardiogenic shock are less well established, with a target MAP of 65 mmHg with the use of vasopressors and/or inotropes being extrapolated from studies of septic or vasoplegic shock. The American College of Cardiology/American Heart Association Scientific Statement highlights that no clear blood pressure or MAP recommendations can be made because of limited data.²⁶

A MAP target of 65 mmHg in cardiogenic shock is weakly supported by a single study by Burstein et al who retrospectively reviewed 1,001 cardiogenic shock patients and found that average MAP over the first 24 hours was inversely associated with ICU and in-hospital mortality, even after adjustment for the stage of shock based on the Society for Cardiovascular Angiography & Interventions (SCAI) Shock Stage Classification.²⁷ Among patients with lower MAPs, there was a higher risk of non-cardiovascular organ failure and severe AKI. However, this finding may not reflect a causal relationship, since lower MAP simply may be a marker of more severe illness. The authors observed that patients with cardiogenic shock due to decompensated heart failure seemed to have better clinical outcomes with a MAP above 70 mmHg.²⁷ This finding suggests that there may be different phenotypes in cardiogenic shock, and targeted therapies may need to be considered among the various subpopulations. In a substudy of the CAPITAL DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, there were higher event rates of the composite primary outcome of in-hospital all-cause mortality, cardiac arrest, need for cardiac transplant or mechanical circulatory support, myocardial infarction, transient ischemic attack/stroke, or need for RRT in the lower MAP group (average MAP < 70 mmHg over the first 36 hours) compared to those in the higher MAP group.^28,29 As expected, the vasoactive-inotropic score and serum lactate levels were higher in the low-MAP group. Based on these studies, it remains unclear whether targeting a higher MAP goal in cardiogenic shock results in clinically important benefits or whether a lower MAP is primarily indicative of a poor prognosis.

Conclusion

Data on optimal targets for different states of shock are sparse. Most of the high-quality literature is focused on patients with septic shock. These data have been extrapolated for clinical use in managing shock due to other etiologies. In general, a target MAP > 65 mmHg can be considered as reasonable to maintain organ perfusion in most states of shock. In patients younger than 75 years with septic shock with chronic hypertension, a higher MAP target of 75 mmHg to 85 mmHg could be considered. In patients with penetrating trauma, permissive hypotension should be targeted until control of hemorrhage is achieved. TBI and SCI are complex clinical situations that mandate considering CPP and SPP as part of ICU management. In cardiogenic shock, a target MAP > 65 mmHg is potentially reasonable given no clear guidelines, although different phenotypes (e.g., decompensated heart failure) may require different targets for better outcomes.

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