Congress report Schweiz Med Wochenschr 2000;130:1516–24 U. Kreimeier, S. Prueckner, K. Peter Permissive hypotension1 Department of Anaesthesiology, Klinikum Grosshadern, Ludwig-Maximilian University, Munich (D) Summary In trauma patients restoration of intravascular period is intentionally prolonged until opera- volume in an attempt to achieve normal sys- tive intervention) and “permissive hypoten- temic pressure faces the risk of increasing sion” (where restrictive fluid therapy increases blood loss and thereby potentially affecting systemic pressure without reaching normoten- mortality. Due to the lack of controlled clini- sion). In this review the concept of “permissive cal trials in this field, the growing evidence that hypotension” is delineated on the basis of hypotensive resuscitation results in improved macro- and microcirculatory changes sec- long-term survival mainly stems from experi- ondary to hypovolaemia and low driving pres- mental studies in animals. The main differences sure, and the potential indications and limita- between concepts for the reduction of blood tions are discussed. loss in systemic hypotension are between “de- Keywords: permissive hypotension; hypoten- liberate hypotension” (synonym “controlled sive resuscitation; primary resuscitation; hypotension”, used intraoperatively), “de- trauma care; fluid therapy; brain injury layed resuscitation” (where the hypotensive Zusammenfassung Bei Patienten nach Trauma und Schock ist die potensive Intervall bewusst bis zur operativen Steigerung des Intravasalvolumens zwecks Er- Versorgung verlängert wird) und «permissive zielung einer Normotension mit dem Risiko hypotension» (wobei mittels restriktiver Flüs- eines erhöhten Blutverlusts und damit mögli- sigkeitstherapie zwar der systemische Druck cherweise mit einem (negativen) Einfluss auf erhöht wird, ohne allerdings normotensive die Überlebensrate verbunden. In Ermange- Werte zu erreichen). In dieser Übersicht wird lung kontrollierter klinischer Studien zu die- das Konzept der permissiven Hypotension auf sem Thema legen bislang vor allem die Ergeb- der Grundlage der infolge Hypovolämie und nisse tierexperimenteller Untersuchungen niedrigem Perfusionsdruck eingetretenen Ver- einen positiven Effekt auf die Überlebensrate änderungen von Makro- und Mikrozirkula- mittels «hypotensive resuscitation» nahe. Bei tion erläutert und mögliche Indikationen und den Konzepten zur Verminderung des Blutver- Limitierungen dieser Methode diskutiert. lusts in Anwesenheit einer systemischen Hypo- Keywords: permissive Hypotension; hypoten- tension ist zu unterscheiden zwischen «deli- sive Reanimation; primäre Reanimation; Trau- berate hypotension» (Synonym: «controlled mabehandlung; Flüssigkeitstherapie; Gehirn- hypotension», die intraoperativ angewandt verletzung wird), «delayed resuscitation» (wobei das hy- Correspondence: PD Dr. med. U. Kreimeier, MD Department of Anaesthesiology Klinikum Grosshadern Ludwig-Maximilian-University 1 Main lecture presented at the Annual meeting of the Swiss Society of Intensive Care with participation Marchioninistrasse 15 of the Swiss Society of Medical Informatics D-81377 Munich (Davos, September 23–24, 1999) e-mail: [email protected] 1516 Schweiz Med Wochenschr 2000;130: Nr 42 Congress report Introduction The present review focusses on the manage- mortality. The concept of permissive hypoten- ment of the polytraumatised patient in view sion is delineated on the basis of macro- and of pathophysiologic alterations induced by microcirculatory changes secondary to hypo- trauma and shock. Restoration of intravascu- volaemia and low driving pressure, and the lar volume in an attempt to achieve normal potential indications and limitations are dis- systemic pressure faces the risk of increasing cussed. blood loss and thereby potentially affecting Defining the problem In recent years there have been increased ac- that hypotensive resuscitation results in im- tivities in the prehospital management of proved long-term survival [1–4]. To date, the trauma and shock and a trend towards early only published study in humans, in victims of and aggressive intervention. While logistics penetrating torso trauma, has demonstrated a have been improved and therefore the time in- significant reduction in mortality when fluid terval until arrival of the emergency team at the resuscitation was restricted in the prehospital accident site has been shortened, issues of de- period [5]. However, it is important to note bate have been prehospital airway manage- that the objective of that study was the com- ment and fluid resuscitation. parison between standard prehospital and Many trauma victims show signs of hypovo- trauma centre fluid resuscitation versus de- laemia and shock in conjunction with tissue layed onset of fluid resuscitation, i.e. having injury, and there has been an ongoing contro- vascular catheters placed but i.v. fluid not ad- versy whether or not to perform early aggres- ministered until patients reached the operating sive fluid replacement therapy. While restora- room. Moreover, the mean length of time from tion of intravascular volume and pressure is injury to arrival in the operating room was re- intuitively logical, attempts to achieve normal markably short in both groups. Thus, clinical arterial pressure during uncontrolled bleeding data from well controlled, prospective trials will increase blood loss. In contrast, from ex- applying the concept of permissive hypoten- perimental studies there is growing evidence sion in trauma patients are still missing. Consequences of trauma and blood loss Hypovolaemia affects myocardial perfor- MAP falls below 75 mm Hg. At this level, per- mance predominantly through the decrease in fusion is still sufficient to meet the metabolic cardiac output via the Frank-Starling mecha- needs of the kidneys cells, although oliguria nism. Minor losses up to 10% of blood volume may ensue. These data, however, stem from ex- are generally compensated by a slight increase periments in which blood pressure was low- in heart rate leaving cardiac output and system- ered pharmacologically, i.e. normovolaemia ic blood pressure unaffected. With increasing was maintained (see below: “deliberate hypo- volume loss and a concomitant decrease of tension”). When challenging the autoregula- venous return, a fall in cardiac output occurs. tory threshold, one has to take into account po- If hypovolaemia exceeds 20% of normal in- tentially preexisting alterations relevant for travascular volume, the heart rate substantially blood flow in organs, for example diabetes, increases, and peripheral vasoconstriction and atherosclerosis, or other vascular abnormali- a decrease in systolic pressure develop [6]. ties compromising total inflow under normal Blood flow to the skin and peripheral tissues is circulatory conditions (e.g. renal or carotid ar- reduced in an effort to preserve perfusion of tery stenosis). vital organs. In response to hypovolaemia the distribution Even in organs with autoregulatory response of cardiac output to the organs is rearranged to a variation in blood pressure shifts of intra- depending on their α- and β-adrenergic inner- organ blood flow occur, which are relevant for vation [7]. Due to the high α-adrenergic inner- organ function particularly in case of underly- vation of the splanchnic vascular bed, blood ing disease. With regard to the kidney, e.g. flow to the intestine and to the gut mucosa in glomerular filtration rate is maintained until particular are curtailed, and early failure of in- 1517 Congress report Schweiz Med Wochenschr 2000;130: Nr 42 testinal barrier function further contributes to loss of intestinal mucosal barrier function with the process of protracted shock states. Even ensuing translocation of bacteria and endo- short phases of low flow as result of trauma toxins with the release of cytokines (TNF α, and shock can induce lesions of the gut mucosa IL-1, IL-6) and postanoids (PGE2) [9]. [8], and represent one of the key factors for the Alterations at the microcirculatory level secondary to low perfusion pressure and shock The two major factors responsible for the scious hamster model indicate that response of decrease in nutritional blood flow following the small arteries is the crucial determinant of trauma and shock are hypovolaemia and low blood flow at the microcirculatory level, and perfusion (driving) pressure. The balance be- constriction of these vessels may help sustain tween total oxygen delivery and oxygen de- arterial pressure, while constriction of small mand is maintained as long as tissue oxygen veins may enhance blood redistribution from extraction can be enhanced while nutritional the skin to the vital organs under the hypoten- blood flow decreases as result of blood loss. sive condition. The recovery of blood flow, However, beyond a critical point tissue perfu- oxygenation, and functional capillary density sion can no longer meet the local oxygen needs. (the latter describing the number of capillaries The consequences are anaerobic metabolism, with RBC flow stemming from a small arte- cellular acidosis, and impairment of specific riole) following haemorrhagic shock and re- organ function favouring the development of suscitaton depends not only on blood oxygen multiple organ failure (fig. 1) [10]. content, but also on the viscosity of the circu- The normal microvascular perfusion is charac- lating blood and the heterogenous shear stress- terised by temporal and local variations of dependent production of endothelium-derived