The BAT and the SOFA! The 3rd Consensus Definitions for Sepsis are out

Picture
Sepsis certainly keeps us going... either when treating patients on ICU or when it comes to the discussion on what actually sepsis is and how to define it. So far the SIRS (Systemic Inflammatory Response Syndrome) criteria have provided some degree of handle to cope with this syndrome but of course we weren't all quite happy with this. In fact every person with any sort of infectious disease will respond with 2 or more SIRS criteria... but doesn't necessarily have to be septic. As a matter of fact a SIRS is nothing else but a physiologic response to any sort of inflammation.


The New Approach to Sepsis - The SOFA

The new international consensus definitions for sepsis and septic shock try to focus on the fact that sepsis itself defines
a life-threatening organ dysfunction caused by a dysregulated host response to infection. By saying this the aim is to provide a definition that allows early detection of septic patients and allow prompt and appropriate response. As even a modest degree of organ dysfunction is associated with an increased in-hospital mortality the SOFA score (Sequential or 'Sepsis-related' Organ Failure Assessment) was found to be the best scoring system for this purpose. It's well known, simple to use and has a well-validated relationship to mortality risk.

Sepsis (related organ dysfunction) is now defined by a SOFA score of 2 points or more



The Quick Approach to Sepsis - The BAT

In the out-of-hospital setting, on the general wards or in the emergency department the task force recommends an altered bed side clinical score called the quickSOFA - or alternatively 'the BAT' score:


The New Approach to Septic Shock -Vasopressors and Lactate

Septic shock is now defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of death than sepsis alone. Keeping a long story short:


Septic Shock is now:

- The need for vasopressors to maintain a mean arterial pressure of at least 65mmHg 
  AND
- a serum lactate level of more than 2mmol/L... after adequate fluid resuscitation 



The Bottom Line:

The way it looks like we are left with Sepsis and Septic Shock


Severe Sepsis has vanished and the question remains, whether these new definitions will actually benefit the ones that need it most... our septic patients!


Singer M et al. JAMA. 2016;315(8):801-810.

Seymour CW et al. 
JAMA. 2016;315(8):762-774.

Shankar-Hari M et al.  
JAMA. 2016;315(8):775-787.

The Myth of Cricoid Pressure – A Correspondence Worth Reading

Picture
One of the most controversial manoeuvres in anaesthesia and critical care has got some new support since the Difficult Airway Society has published their new guidelines in which they basically continue to support the use of cricoid pressure (CP) for rapid sequence induction. The authors of the Obstetric Anaesthetists' Association and Difficult Airway Society Guidelines for the Management of Difficult and Failed Tracheal Intubation also continue to recommend routine CP, which is considered level 3b evidence.

Surprised on how obstinately CP persists in current guidelines I think that following statement by Priebe HJ is an important reading. It summarises nicely why there is such a disagreement with these recommendations.


He states that

not a single controlled clinical study provided convincing evidence that the use of cricoid pressure was associated with reduced risk of pulmon ary aspiration. At the same time, there is good evidence that nearly all aspects of airway management are adversely affected by cricoid pressure

-  if
cricoid pressure were considered a new airway device, it would not be considered for further evaluation because Level 3B evidence for its efcacy does not exist

- when
using cricoid pressure, we may well be endangering more lives by interfer ing with optimal
airway management than we are saving lives by preventing pulmonary
aspiration

Priebe HJ, Anaesthesia 2016, 71, 343–351


Want to get more information on the controversy of cricoid pressure? Read here:

Cricoid Pressure for RSI in the ICU: Time to Let GO?


Time to let go? Remarkable article on RSI and Cricoid Pressure


Difficult Airway Society DAS: New Guidelines OUT! Cricoid Pressure still IN?

Dexmedetomidine vs Midazolam for the Intubated

Picture
Dexmedetomidine has shaken up the usual sedatives in ICU but remains a matter of debate among intensivists. One question is whether the higher costs compared to midazolam are justified by clinical advantages. There is research available suggesting that dexmedetomidine might be an attractive alternative to standard sedatives especially in regards of time to extubation and costs (Turinen et al., Jacob et al.). This seems to hold true for moderate to light sedation of intubated patients.

I've stepped over this prospective, double-blind, randomised trial by Riker et al. in which 68 centres in 5 countries recruited intubated 366 patients to received moderate to light sedation with either dexmedetomidine or midazolam. All patients received daily arousal assessment. 

Their primary end point was the percentage of time within the target sedation range (RASS score −2 to +1) and this did not differ between the two groups.

Looking at the secondary endpoints though make things a lot more interesting. Just before the beginning of the 
sedation period both groups had a similar prevalence of delirium. During study drug administration though, the effect of dexmedetomidine treatment on delirium was significant. A reduction of 24.9% with dexmedetomidine is rather impressive (see figure below). This effect was even greater in patients who were CAM-ICU-positive at baseline.

Finally patients on dexmedetomidine had shorter time to extubation (1.9 days in average) while their length of stay on ICU did not differ.

From a safety point of view the most common adverse effect of dexmedetomidine was bradycardia. It's noteworthy that patients on midazolam had more episodes of hypotension and tachycardia.

THE BOTTOM LINE

- This is another study indicating that dexmedetomidine seems to be beneficial in regards of delirium in mechanically ventilated patients and might speed up time to extubation

- Dexmedetomidine is safe in patients where moderate to light sedation is the aim



Riker et al. JAMA. 2009;301(5):489-499. doi:10.1001/jama.2009.56     OPEN ACCESS


Read more HERE on BIJC

Lactate – From Bad to Good? An Explanation Trial

Picture
The discussion on the so called lactic acidosis and its causes has become increasingly interesting over the last couple of years as several biochemical explanations have been challenged. A big confusion persists on the various relationships between lactate, lactic acid and metabolic acidosis. 

Most clinicians continue to refer to the classical understanding of impaired tissue oxygenation causing increased lactate production, impaired lactate clearance and therefore resultant metabolic acidosis. Just recently we had a discussion on our ward round on this topic when I was presented the most recent article of UpToDate online on the causes of lactic acidosis. The authors state that 'Lactic acidosis is the most common cause of metabolic acidosis in hospitalised patients' and that 'Lactic acidosis occurs when lactate production exceeds lactate clearance. The increase in lactate production is usually caused by impaired tissue oxygenation...'... finally suggesting that lactate is no good!

These statements support the classical understanding that:
- Hyperlactatemia is caused by tissue hypoxemia, and
- This in turn then leads to a metabolic acidosis called lactic acidosis


This biochemical understanding has persisted for decades but there are some good reasons to strongly challenge this classical aspect on the 'bad' lactate. Lactate turns out to be by far more complex in its characteristics and functions, so I decided to try and make a short but comprehensive overview on this molecule.

What is lactate?

Picture
Lactate is a small organic molecule with the chemical formula CH3CH(OH)CO2H and structurally looks like on the image to the left. It is produced in the cytoplasm of human cells largely by anaerobic glycolysis by the conversion of pyruvate to lactate by LDH. This chemical reaction normally results in a blood lactate to pyruvate ratio of about 10:1. And while lactate is produced, NAD+ also is incurred and this actually can accept protons itself, so does not result in acidosis itself.

Lactate arises from the production of energy by consuming glycogen and glucose.


​Where does it come from?

Picture
Typically most people think of muscles first as an origin of lactate. As a matter of fact lactate originates from many other organs, including our red blood cells. Red blood cells always produce lactate as they lack the mitochondria required to regenerate NAD+ needed for glycolysis.  In general you can say that tissues with lots of LDH are the main producers of lactate. Around 20mmol/kg/day of lactate are produced under normal circumstances.

Lactate is not only produced in skeletal muscle.

Muscle: 25%
Skin: 25%
Brain: 20%
RBC: 20%
Intestine: 10%

What happens with it?

Lactate is not just for nothing. After its production by anaerobic glycolysis lactate is reutilised, for instance in the liver and the cortex of the kidneys. As an example: under the influence of cortisol it is used for gluconeogenesis in hepatocytes and restores glucose and glycogen. Also it is a part of oxidative phosphorylation in the liver, kidney, muscles, the heart and the brain. Like this lactate helps conserve glucose levels in our blood.

​Lactate actually serves as a fuel for oxidation and glucose regeneration and therefore is a source for energy itself.
Picture
From The Lancet Endocrinology 2013



​How does hyperlactatemia develop?

In general you can assume that there is a balance between lactate production and its consumption or usage. The classical understanding that tissue hypoxia leeds to overproduction and underutilisation by impaired mitochondrial oxidation is basically correct.

The key point though is that lactate is also produced via aerobic glycolysis as a response to stress. This happens in septic patients, asthmatic exacerbations, trauma and other critical conditions. In these situations the trigger for lactate production is adrenergic stimulation and NOT tissue hypoxia. There are also several other reasons for hyperlactatemia other than tissue hypoxia:


Sepsis:      Adrenergic drive
Asthma:    Adrenergic drive
Trauma:    Adrenergic drive
Cardiogenic and haemorrhagic shock: Adrenergic drive
Pheochromocytoma: Adrenergic drive
Inflammation: Cytokine drive
Alkalosis, antiretroviral medication and others


Also, there is good evidence showing that organs like the lungs are an important producer of lactate during stress. And of course in all these conditions hypoxic and non-hypoxic hyperlactatemia might also co-exist.

In critically ill patients often other reasons than tissue hypoxia are responsible for hyperlactatemia (e.g. adrenergic drive).

Is lactate harmful?

In contrast to the classical understanding of lactate and lactic acidosis more and more evidence comes up indicating that lactate during stress actually serves as a fuel for energy production. Various tissues, e.g. the myocardium increase their lactate uptake during stress significantly. Also our brain consumes more lactate during stress which is used for oxidation. Research has shown that lactate infusions improve cardiac output in pigs and even in patients with heart failure. 

Experimental work on isolated muscles suggests that circulating catecholamines and development of acidic conditions during exhaustive exercise may improve muscles' tolerance to elevated K+ levels. This implies that during high-intensity activity with high extracellular K+
 and adrenaline, lactate actually serves as a performance-enhancing chemical, rather than being the cause of muscle fatigue.

Lactate is not harmful for our organism. On the contrary, recent compelling evidence actually suggests that lactate might actually be beneficial, rather than detrimental, during high-intensity activity and to force development in working heart and skeletal muscle.

Why do critically ill patients with hyperlactatemia die more often then?

In critical care hyperlactatemia indeed is a marker of illness severity and a strong indicator of mortality. This is especially true for patients with sepsis. However, as described above, hyperlactatemia often doesn't indicate hypoperfusion or tissue hypoxia. Hyperlactatemia rather reflects the severity of illness by representing the degree of our body's activation to stress. A fall in lactate concentration following treatment of critically ill patients is due to an attenuation of the stress response rather than to correction of oxygen debt.

Hyperlactatemia reflects severe disease and the patients response to stress. Patients die due to their illness, not because of a high lactate.

What about Ringer's lactate?

Picture

Ringer's lactate (RL) is not harmful in patients with hyperlactatemia.

As a matter of fact RL turns out to be superior compared to normal saline in hyperlactatemia, acidotic patients and patients with hyperkalemia.

The bottom line

- Lactate is an indicator of stress, a marker of illness severity and a strong predictor of mortality, but not harmful as a molecule itself.

- Lactate is helpful
 as an important source of energy and an important fuel for oxidation and glucose generation.

- During conditions like septic shock there is no proof that lactate is produced only due to tissue hypoxia. In fact well ventilated lungs produce a large amount of lactate during sepsis. Lactate in sepsis and other critical conditions is mostly not due to hypoxemia or hypoperfusion.

- Ringer's lactate contains sodium lactate, but not lactic acid. Lactate itself, as mentioned above, is actually beneficial in severe disease. Therefore RL remains the fluid of choice during severe disease like for instance septic shock.

- Ringer's lactate is superior to normal saline in patients with metabolic acidosis, hyperlactatemia and also hyperkalemia.
Picture
Click in image to listen to podcast

Analgosedation with Ketamine in the ICU: What is the Evidence?

Picture
Ketamine's success seems unstoppable:
​+++ 
Anaesthesiologists are opening private clinics for off-label infusions of ketamine for depression http://bit.ly/1IGYTcI +++ Dr. Jim Roberts says #ketamine is an ideal treatment for excited #delirium: http://emn.online/Dec15InFocus +++ Major #ketamine treatment trial to start in 2016 http://m.huffpost.com/au/entry/8501942 +++ More impressed every day with low dose ketamine for pain management! https://www.youtube.com/watch?v=DgckjVVBb48 ...

Intravenous ketamine is also used in critical care units and to my knowledge most clinicians use ketamine as an adjunct to other sedatives. This might be for patients on mechanical ventilation, intubation procedures or simply as an additive to a patient-controlled analgesia pump. I personally think ketamine is one of the essentials in ICU's, but what does the evidence say. 

Asad et al. have performed a systematic review on the usage of ketamine as a continuous infusion (>24h) in intensive care patients. The aim was to find evidence in favour for the utilisation of ketamine in the ICU.


As a result of this review - current evidence suggests that:

- In critically ill postoperative patients ketamine has the potential to reduce the cumulative morphine consumption at 48h compared to morphine only

- Several trials show the potential safety of ketamine in regards of cerebral haemodynamics in patients with traumatic brain injury, improved gastrointestinal motility and decreased vasopressor requirements

- One observational study and case reports suggest that ketamine is safe, effective and 
may have a role in patients who are refractory to other therapies


​Our conclusion: THUMBS UP for ketamine in the ICU



Asad E. et al. 
J Intensive Care Med December 8, 2015