Iatrogenic salt water drowning and the hazards of a high central venous pressure.

Marik Annals of Intensive Care 2014, 4:21

Paul Marik has been investigating the effects of fluid on the septic patient over the years, publishing several important papers in the process.

Does Central Venous Pressure Predict Fluid Responsiveness? CHEST 2008

Heamodynamic parameters to guide fluid therapy. Annals of Intensive Care 2011

Does the Central Venous Pressure Predict Fluid Responsiveness? An Updated Meta-Analysis and a Plea for Some Common Sense. Crit Care Med. 2013

He opens his paper by first of all discussing some of the dangers of large volume fluid resuscitation. These seem to be many;

• The septic heart responds poorly to fluid loading, as the Frank Starling curve is shifted downwards into the right. (Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock. CHEST 1998)
• Large volume fluid resuscitation causes only a small increase in/volume at the expense of large increases in filling pressures.
• Increased endothelial permeability and an increased vasodilation due to the release of natriuretic peptides results in fluid moving into the interstitium. (Broken barriers: a new take on sepsis pathogenesis. Sci Transl Med 2011) (Atrial natriuretic peptide induces shedding of endothelial glycocalyx in coronary vascular bed of guinea pig hearts. Am J Physiol Heart Circ. 2005)

• Increased filling pressures and a positive fluid balance will also increase extract vascular lung water which will in turn impair gas exchange and increase the work of breathing. (Fluid management in critically ill patients: the role of extravascular lung water, abdominal hypertension, capillary leak, and fluid balance. Annals of Int Care. 2012)
• As a consequence of these issues less than 5% of infused crystalloid remains intravascular within three hours after infusion. (Importance of the infusion rate for the plasma expanding effect of 5% albumin, 6% HES 130/0.4, 4% gelatin, and 0.9% NaCl in the septic rat. Crit Care Med 2013)
• This increases tissue oedema which can then have effects on other organs such as the liver and kidneys. (Fluid balance and acute kidney injury. Nat Rev Nephrol. 2010)
• This may then lead to acute kidney injury and hepatic congestion.
• Bowel oedema may also then result in malabsorption.
• Multiple clinical studies have demonstrated an independent association between an increasingly positive fluid balance and increased mortality in patients with sepsis. (Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011)
• Aggressive fluid loading may be associated with a significantly increased risk of death. (Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial. 2013)
• Fluids alone will not reverse the hemodynamic instability of patients with more severe sepsis; in these patients’ fluids alone are likely to exacerbate the vasodilatory shock and increase the capillary leak, tissue edema and organ dysfunction. (Selective V_1a agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis. Am J of Physiol. 2012)
• There is now mounting evidence that the amount of fluid used in early goal directed therapy was possibly excessive. (Goal-Directed Resuscitation for Patients with Early Septic Shock ARISE. NEJM 2014; A Randomized Trial of Protocol-Based Care for Early Septic Shock. ProCESS. NEJM. 2014)
• In trauma patients high volume fluid resuscitation has now given way to a damage control strategy which has seen a fall in the volume of crystalloid delivered in the emergency department. ( Early fluid resuscitation in severe trauma. BMJ 2012; Liberal versus restricted fluid resuscitation strategies in trauma patients: a systematic review and meta-analysis of randomized controlled trials and observational studies. Crit Care Med. 2014).

Marik concludes here by saying that the only piece of research which seems to support aggressive fluid resuscitation is that by Rivers (Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. NEJM 2001) which proposed early goal directed therapy. He goes on to present some evidence which highlights some of the flaws in this study.

He then goes on to highlight some of the dangers of a high CVP:

• CVP has failed as a useful measure of preload and fluid responsiveness (Does the Central Venous Pressure Predict Fluid Responsiveness? An Updated Meta-Analysis and a Plea for Some Common Sense. Crit Care Med. 2013)
• A normal CVP is close to 0 and not 8 to 12 mmHg as the surviving sepsis campaign says. (Does not quote any evidence for this).
• Marik uses the figure mean circulatory filling pressure (MCFP) which is defines as the driving pressure that determines venous return and is considered synonymous with the effective circulating blood volume. This is normally in the range of 8 to 10mmHg. (The role of venous return in critical illness and shock-part I: physiology. Crit Care Med. 2013)

• A study which investigated the relationship between the changes in the MCFP and the change in the CVP and/volume following a fluid challenge seem to indicate that a disproportionate increase in the CVP will impede venous return and cardiac output. (The role of venous return in critical illness and shock-part I: physiology. Crit Care Med. 2013).
• A high CVP can also cause back pressure in the venous circulation which can have some effects on the glomerular filtration rate. In recent studies a linear relationship between increasing CVP and AKI has been demonstrated with the higher CVP being associated with a worse renal outcome. (Association between systemic hemodynamics and septic acute kidney injury in critically ill patients: a retrospective observational study. Crit Care. 2013).
• Those patients with acute decompensated heart failure demonstrated an almost linear relationship between increasing CVP and worsening renal function. (Importance of Venous Congestion for Worsening of Renal Function in Advanced Decompensated Heart Failure. J Am Coll Cardiol. 2010).
• There is data suggestive of a high CVP increasing the risk for congestive kidney failure. A consequence of this is that fluid loading patients with oliguria may well set into motion a vicious cycle with a further decline in renal function. (Relationship between fluid status and its management on acute renal failure (ARF) in intensive care unit (ICU) patients with sepsis: a prospective analysis. J Nephrol. 2005).
• The high CVP can also cause an increase in hepatic and intestine all venous pressure causing hepatic and intestine or congestion.

The dangers of normal saline are the next point of discussion.

• Chloride Liberal fluid resuscitation was associated with a much higher incidence of renal failure than those patients resuscitated with chloride restrictive fluid. (Association between a chloride-liberal versus chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adult. JAMA 2012).
• Hyperchloreamic metabolic acidosis has been demonstrated in patients resuscitated with normal saline. This state is an independent predictor of death. (Is hyperchloremia associated with mortality in critically ill patients? A prospective cohort study. J Crit Care 2011).
• LR may have additional advantages in shocked patients with the lactate being oxidized and serving as a source of energy. (Stress hyperlactemia. Lancet Endo Diabetes. 2013.; Is Hartmann’s the solution? Anaesthesia. 2004)

“A liberal fluid resuscitation strategy, a CVP less than eight and the use of normal saline as the predominant resuscitation fluid are all associated with an increased risk of renal failure, respiratory failure, gastrointestinal dysfunction and death across a broad spectrum of clinical disorders. These three treatment strategies probably act synergistically to harm patients, forming the “Deadly Trio“.

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