Intravenous fluids (IV fluids) are routinely used to restore effective blood volume and maintain organ perfusion during resuscitation. Optimal dose and type of IV fluids to be used during resuscitation is still an area of debate and may therefore be responsible for significant variability in global resuscitation practices.

• Surviving sepsis campaign recommended 30ml/kg for patients in septic shock
• fluid responsiveness is an important concept
  • fluid bolus - a therapeutic volume of fluid used as an intervention
  • fluid challenge - a diagnostic volume of fluid to test assessment

Assessments of 'fluid volume' have included - CVP and PAP as surrogates for R and L filling pressures, with PAP especially now falling out of favour as offering little extra information. Problems though:

• variable alterations in cardiac contractility either by nature or disease affect filling pressures
• variations with ventilation

• colloids - albumin, starches, gelatins and dextrans
• crystalloids
• blood products

Ongoing debate with the theoretical benefit of high-molecular weight compounds presumed to stay longer in the intravascular space not proving superior.

• Concentrated albumin may have the added benefit in some circumstances of conferring benefits of enhanced immunity.
• Endogenous albumin exhibits antioxidant effects, scavenges free radicals, serves as a critical transport protein for many molecules and medications, and may modulate inflammatory response

• group of semi-synthetic colloids prepared by hydroxyethylation of amylopectin from sorghum, corn, or potatoes
• early starches were toxic primarily related to coagulation and accumulation. Later starches much better.
• no clear benefit compared with crystalloid

• various with different amounts of K+, Cl-, Mg++, Lactate etc
• Cl- rich solutions have been shown to induce renal art vasoconstriction, AKI, hyperchloraemic acidosis, GI dysfunction and secretion of inflammatory cytokines.
• One of the key differences between 0.9 % saline and buffered/balanced crystalloids is the presence of additional anions, such as lactate, acetate, malate and gluconate, which act as physiological buffers to generate bicarbonate.
• acetate has been associated with a reduction in myocardial contractility and vasodilation
• According to the Stewart physiochemical approach to describing acid‐base balance, fluid pH is in part determined by the SID, which is the sum of the strong cation concentrations in the solution. Extracellular fluid has a SID of 40mEq/l. Saline =0, Ringer's lactate and Hartmann's (both hypotonic solutions) are 28 & 27.
• risk of Ca++ containing solutions (Ringer's, Hartmann's) causing precipitation and coagulation when mixed with blood products and causing ceftriaxone to form an insoluble salt.

• produces a transient increase in Na+, while its buffering action raises serum & urine pH
• especially useful in TCA overdose - by raising serum pH, increases non-ionised drug, decreases binding to Na+ channels
• aspirin overdose - alkalises urine which enhances elimination

Beneficial in settings where there is Na bicarb loss eg diarrhoea and renal tubular acidosis but treatment of 'the no.' in other conditions has not been shown to improve outcome or mortality. In particular, settings in which IV bicarb does NOT improve outcomes include DKA, lactic acidosis, septic shock, cardiac arrest and intraoperative metabolic acidosis.
Problems include:

• hypernatraemia and hyperosmolality with vasodilation and haemodynamic instability
• hypercapnia
• rebound alkalosis
• hypokalaemia and ionised hypocalcaemia
• prolonged QTc
• CSF acidosis

• 2 acetate anion forms acetyl CoA and enters the citric acid cycle; the final by-products, CO2 and H2O, are in a rapid equilibrium with bicarbonate through the catalyst activity of carbonic anhydrase.
• Na acetate is less reliant on carbonic anhydrase for the alkalaemia it causes and is metabolised to a great extent in skeletal M.
• more dangerous in higher doses used in dialysis (myocardial depression and hypotension)

diabetic ketoacidosis (DKA)
Septic Shock

Not enough clinical evidence to unequivocally recommend one agent over another in every clinical scenario, although some have more generally accepted preferential use, eg. NorAdrenaline as the initial vasopressor as per Surviving Sepsis Campaign (Septic Shock) and generally in Neurogenic Shock associated with spinal pathology. The literature will ascribe different weightings of action of various agents on each receptor. eg. Adrenaline said to be more β than ∝ in some and equivocal in others. The table included here is an example of one comparison of affinity and preferential setting.

Relevant receptors:

• β1: mostly chronotropic and inotropic effects
• β2: mostly chronotropic and vasodilatory
• ∝: peripheral vasoconstriction
• V₁: smooth muscle contraction of vessels
• V₂: collecting tubule receptor - regulates water retention
• dopaminergic: renal artery vasodilation

increase myocardial contractility

• adrenaline
  • ∝ & >β
  • β1 +ve inotropy, chronotropy and β2 vasodilation and bronchodilation. ∝1 increases SVR
• dobutamine
  • synthetic catecholamine
  • β1 > β2
  • +ve inotropy and chronotropy
  • tendency to cause tachyarrhythmias
• isoprenaline
  • β1 & β2
  • very powerful chronotrope
  • pure β and doesn't cause vasoconstriction, so peripheral IV use is possible
• ephedrine
  • ∝ & β
  • +ve inotropy, both vasodilation and vasoconstriction with vasoconstriction at higher doses
  • direct ∝ action as well as indirect action displacing NorAdrenaline, which also therefore causes Tachyphylaxis.
  • similar to adrenaline but lasts longer
  • used especially during pregnancy as does not significantly affect uterine flow

vasoconstrictors cause increased systemic and/or pulmonary vascular resistance (SVR, PVR)

• noradrenaline
  • β & >∝
  • increases SVR. β effects at higher doses
  • commonly used in septic shock
• vasopressin
  • V₁, V₂ and V₃ agonist as well as OTR (oxytocin rec)
  • vasoconstriction (V₁ rec), renal water retention (V₂ rec), ↑ACTH (V₃ rec in pituitary) and vasodilation (OTR rec breast, uterus, aorta, pulm art)
  • does cause some venoconstriction thereby increasing venous return (preload)
  • useful in septic shock
• metaraminol
  • ∝ & weak β
  • direct ∝ action and indirect action to displace NorAdrenaline, which also therefore causes Tachyphylaxis.
  • commonly used to increase SVR in hypotension related to anaesthesia
  • IV bolus: 0.5-5mg
• terlipressin
  • synthetic, long-acting analogue of vasopressin with t_1/2 of 6/24 compared with vasopressin 6mins
  • common use - oesophageal varices
  • Dose: initial 1-2mg depending on weight, then 1mg per 4-6/24
• methylene blue
  • inhibitor of nitric oxide synthase and guanylate cyclase
  • useful in vasoplegia associated with various drugs, eg. Heparin, ACE inhibitors, CCF etc
  • also useful in Hepatorenal Syndrome in which pulmonary vasodilation is thought secondary to ↑cGMP
  • also useful in Methaemoglobinaemia amongst other conditions
  • Dose: 1.5-2mg/kg over 20mins

inotropic effects with vasodilation

• milrinone
  • phosphodiesterase inhibitor increases intracellular cAMP
  • inotrope and vasodilator
  • commonly used in cardiac failure
  • Dose: 50mcg/kg initial, infusion @ 0.375-0.75mcg/kg/min
• levosimendan
  • increases cardiac contractility by Ca sensitisation of Troponin C
  • vasodilator and cardiac protection by opening of sarcolemmal and mitochondrial K+ ATP channels, respectively
  • Dose: 3-36mcg/kg initial, infusion @ 0.05-0.6mcg/kg/m

• dopamine
  • precursor of adrenaline and noradrenaline
  • inotrope and vasopressor
  • falling out of favour

• reasons for Intubation in the Emergency setting:

1. inadequate oxygenation by other non-invasive methods eg lung pathology
2. inadequate ventilatory drive eg. neuromuscular pathology
3. inadequate airway patency eg. local physical pathology/trauma
4. imminent potential for any of the above

Fluid Mx of critically ill - 2016
Critical Care - Crystalloid Fluid therapy 2016
Review - Sodium acetate and Bicarb in Toxicology. 2013
Inotropes and Vasopressors 2020
https://litfl.com/inotropes-vasopressors-and-other-vasoactive-agents/
https://litfl.com/sodium-bicarbonate-use/
Review: Bicarb use in Metabolic acidosis 2014
https://emcrit.org/ibcc/pressors/
http://www.anaesthesia.med.usyd.edu.au/resources/lectures/pforrest/Vasopressor%20lecture%20-Part%201.htm
vasopressin and terlipressin in septic shock 2005
Levosimendan - review 2013
Methylene blue review 2010
alternatives to RSI using ketamine W J Emerg Med 2019