Blood Pressure Targets For Vasopressor Therapy: A Systematic Review

ABSTRACT Physicians often prescribe vasopressors to correct pathological vasodilation and improve tissue perfusion in patients with septic shock, but the evidence to inform practice on vasopressor dosing is weak. We undertook a systematic review of clinical studies evaluating different blood pressure targets for the dosing of vasopressors in septic shock. We searched MEDLINE, EMBASE, CENTRAL (to November 2013), reference lists from included articles, and trial registries for randomized controlled trials (RCTs) and observational and crossover intervention studies comparing different blood pressure targets for vasopressor therapy in septic shock. Two reviewers independently selected eligible studies and extracted data on standardized forms. We identified 2 RCTs and 10 crossover trials but no observational studies meeting our criteria. Only one RCT measured clinical outcomes after comparing mean arterial pressure targets of 80 to 85 mmHg versus 65 to 70 mmHg. There was no effect on 28-day mortality, but confidence intervals were wide (hazard ratio, 95% confidence interval [95% CI] 0.84 – 1.38). In contrast, this intervention was associated with a greater risk of atrial fibrillation (relative risk, 2.36; 95% CI, 1.18 – 4.72) and a lower risk of renal replacement therapy in hypertensive patients (relative risk, 0.75; 95% CI, 0.57 – 1.0). Crossover trials suggest that achieving higher blood pressure targets by increasing vasopressor doses increases heart rate and cardiac index with no effect on serum lactate. Our findings underscore the paucity of clinical evidence to guide the administration of vasopressors in critically ill patients with septic shock. Further rigorous research is needed to establish an evidence base for vasopressor administration in this population.

[1]  C. Y. Teng,et al.  Haemodynamic studies in shock associated with infection. , 1967, British heart journal.

[2]  G. Buckberg,et al.  Escherichia Coli Bacteremic Shock in Conscious Baboons , 1971, Annals of surgery.

[3]  K. Rosen,et al.  Acute Hemodynamic Effects of Dopamine in Patients with Shock , 1971, Circulation.

[4]  S. Rahimtoola,et al.  Hemodynamic studies and results of therapy in 50 patients with bacteremic shock. , 1973, The American journal of medicine.

[5]  A. P. Shepherd,et al.  Effect of vasoactive agents on intestinal oxygen consumption and blood flow in dogs. , 1975, The Journal of clinical investigation.

[6]  S. Boley.  Collateral blood flow in segmental intestinal ischemia: effects of vasoactive agents. , 1988, Surgery.

[7]  L. Brinquin,et al.  Autotransfusion après récupération de sang dans les situations d'exception , 1989 .

[8]  [Septic shock: hemodynamic effects of noradrenaline and a noradrenaline-dopexamine combination]. , 1989, Annales francaises d'anesthesie et de reanimation.

[9]  M. Nishimura,et al.  Effects of norepinephrine on renal function in septic patients with normal and elevated serum lactate levels. , 1989, Critical care medicine.

[10]  F. Mosteller,et al.  A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts. Treatments for myocardial infarction. , 1992, JAMA.

[11]  pO2-profiles in human muscle tissue as indicator of therapeutical effect in septic shock patients. , 1992, Advances in experimental medicine and biology.

[12]  P Leppard,et al.  Epinephrine as an inotropic agent in septic shock: A dose‐profile analysis , 1993, Critical care medicine.

[13]  N. Day,et al.  The effects of dopamine and adrenaline infusions on acid-base balance and systemic haemodynamics in severe infection , 1996, The Lancet.

[14]  K. Reinhart,et al.  The effects of low-dose dopamine on splanchnic blood flow and oxygen uptake in patients with septic shock , 1997, Intensive Care Medicine.

[15]  K. Reinhart,et al.  Dopexamine increases splanchnic blood flow but decreases gastric mucosal pH in severe septic patients treated with dobutamine. , 1999, Critical care medicine.

[16]  H. Ehmke,et al.  Autoregulation of renal blood flow, glomerular filtration rate and renin release in conscious dogs , 1987, Pflügers Archiv - European Journal of Physiology.

[17]  R. MacLaren,et al.  Effects of Continuous Vasopressin Infusion in Patients with Septic Shock , 2004, The Annals of pharmacotherapy.

[18]  D. Annane,et al.  Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update , 2004, Critical care medicine.

[19]  L. Oyen,et al.  Fixed‐Dose Vasopressin Compared with Titrated Dopamine and Norepinephrine as Initial Vasopressor Therapy for Septic Shock , 2004, Pharmacotherapy.

[20]  Alan E Jones,et al.  SEVERITY OF EMERGENCY DEPARTMENT HYPOTENSION PREDICTS ADVERSE HOSPITAL OUTCOME , 2004, Shock.

[21]  Claude D Martin,et al.  TERLIPRESSIN IN CATECHOLAMINE-RESISTANT SEPTIC SHOCK PATIENTS , 2004, Shock.

[22]  G. Paret,et al.  TERLIPRESSIN AS RESCUE THERAPY FOR INTRACTABLE HYPOTENSION DUE TO SEPTIC SHOCK IN CHILDREN , 2005, Shock.

[23]  Claude D Martin,et al.  Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. , 2005, Critical care medicine.

[24]  X. Leverve,et al.  EFFECTS OF DOPAMINE AND NOREPINEPHRINE ON SYSTEMIC AND HEPATOSPLANCHNIC HEMODYNAMICS, OXYGEN EXCHANGE, AND ENERGY BALANCE IN VASOPLEGIC SEPTIC PATIENTS , 2005, Shock.

[25]  A. Wechsler-Fördös,et al.  The effects of norepinephrine on hemodynamics and renal function in severe septic shock states , 2005, Intensive Care Medicine.

[26]  D. Dries.  Vasoactive drug support in septic shock. , 2006, Shock.

[27]  O. Gajic,et al.  Liberal vs. conservative vasopressor use to maintain mean arterial blood pressure during resuscitation of septic shock: an observational study , 2007, Intensive Care Medicine.

[28]  Dean E. Myers,et al.  DYNAMIC NEAR-INFRARED SPECTROSCOPY MEASUREMENTS IN PATIENTS WITH SEVERE SEPSIS , 2007, Shock.

[29]  S. Hollenberg.  Vasopressor support in septic shock. , 2007, Chest.

[30]  Sangeeta Mehta,et al.  Vasopressin versus norepinephrine infusion in patients with septic shock. , 2008, The New England journal of medicine.

[31]  G. Guyatt,et al.  GRADE: an emerging consensus on rating quality of evidence and strength of recommendations , 2008, BMJ : British Medical Journal.

[32]  M. Meade,et al.  NITRIC OXIDE DONORS IN SEPSIS: A SYSTEMATIC REVIEW OF CLINICAL AND IN VIVO PRECLINICAL DATA , 2008, Shock.

[33]  E. Ruokonen,et al.  Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial , 2009, Critical care.

[34]  Michele Tarsilla.  Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.

[35]  G. Guyatt,et al.  Systematic review of reviews including animal studies addressing therapeutic interventions for sepsis* , 2010, Critical care medicine.

[36]  A. Mebazaa,et al.  Dopexamine Test in septic shock with hyperlactatemia. , 2010, Annales francaises d'anesthesie et de reanimation.

[37]  L. Azevedo,et al.  HEMODYNAMIC AND PERFUSION END POINTS FOR VOLEMIC RESUSCITATION IN SEPSIS , 2010, Shock.

[38]  G. Patel,et al.  EFFICACY AND SAFETY OF DOPAMINE VERSUS NOREPINEPHRINE IN THE MANAGEMENT OF SEPTIC SHOCK , 2010, Shock.

[39]  D. Noritomi,et al.  ECHOCARDIOGRAPHY FOR HEMODYNAMIC EVALUATION IN THE INTENSIVE CARE UNIT , 2010, Shock.

[40]  S. Hollenberg,et al.  Vasoactive drugs in circulatory shock. , 2011, American journal of respiratory and critical care medicine.

[41]  G. Guyatt,et al.  Vasopressor administration and sepsis: a survey of Canadian intensivists. , 2011, Journal of critical care.

[42]  M. Dünser,et al.  Hemodynamic and perfusion end points for volemic resuscitation in sepsis. Shock 34(Suppl 1):34-39, 2010. , 2011, Shock.

[43]  W. Buurman,et al.  Preventing Enterocyte Damage by Maintenance of Mean Arterial Pressure During Major Nonabdominal Surgery in Children , 2012, Shock.

[44]  D. Chemla,et al.  Effects of norepinephrine on mean systemic pressure and venous return in human septic shock* , 2012, Critical care medicine.

[45]  J. Vincent,et al.  Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis* , 2012, Critical care medicine.

[46]  Taka-aki Nakada,et al.  Normal-Range Blood Lactate Concentration in Septic Shock Is Prognostic and Predictive , 2012, Shock.

[47]  Sang-Bum Hong,et al.  Radial to Femoral Arterial Blood Pressure Differences in Septic Shock Patients Receiving High-Dose Norepinephrine Therapy , 2013, Shock.

[48]  R. Summers,et al.  Characteristics and Outcomes of Patients With Vasoplegic Versus Tissue Dysoxic Septic Shock , 2013, Shock.

[49]  M. Rech,et al.  Racial Differences in Vasopressor Requirements for Septic Shock , 2014, Shock.

[50]  Claude Guerin,et al.  High versus low blood-pressure target in patients with septic shock. , 2014, The New England journal of medicine.

[51]  P. Jorens,et al.  The Duration of Hypotension Determines the Evolution of Bacteremia-Induced Acute Kidney Injury in the Intensive Care Unit , 2014, PloS one.

[52]  B. Fuller,et al.  The Impact of Serial Lactate Monitoring on Emergency Department Resuscitation Interventions and Clinical Outcomes in Severe Sepsis and Septic Shock: An Observational Cohort Study , 2015, Shock.