Septic Shock - Science topic

Hi,

Septic shock is a serious illness, and despite all the advances in medicine, it still carries high mortality, which can exceed 40%. Mortality does depend on many factors, including the type of organism, antibiotic sensitivity, number of organs affected, and patient age.

prognostic factors for Pneumonia: https://www.accjournal.org/upload/pdf/kjccm-2015-30-4-258.pdf

for further organ failure please refer to the proper literature.

I hope, this will help you further...

greatings, Janos

Fluid management is a very complex issue.

There are many confounding factors including co-morbidities such as heart failure, liver disease and renal impairment.

It is important that management is individualised on a case by case basis.

I understand that Roger Seheult, California, has been trying to understand the pathophysiology of Covid -19 based on his reading of the literature, including papers sent to him by others. There are a number of papers that address the value of NAC in treating respiratory illness and the effects of oxidative stress on von Willebrand factor. Roger came up with the idea of treating Covid19 with NAC but in MedCram 70 he notes that Alexey Polonikov, Kursk State Medical University has also reported a series of patients with Covid-19 and sees endogenous deficiency of glutathione as the most likely cause of serious manifestations and death. Polonikov sees oxidative stress as contributing to the hyperinflammation of the lung and poor antioxidant defences as being due to glutathione deficiency. He recommends treatment with N-acetylcysteine and reduced glutathione. Seheult notes that it appears that the impaired lung oxygenation is related in part to thromobosis of pulmonary arterioles because of the von Willibrand factor molecules from platelets adhering to one another. The clots consist of long strands bound to one another by disulphide bonds. The NAC or reduced glutathione break the linked chains apart by breaking up the SS bonds through reducing them by changing them to SH SH so that the chains are no longer linked together. When the clots are lysed with NAC the hypoxaemia may be relieved. Seheult notes that there are different VWF levels in Group O patients and some racial groups (higher in Americans of African heritage). SARSCoV2 can cause a550% increases in VWF levels and the NAC can reduce this. Polonikov measured the Reactive Oxygen Species/Glutathione ratio. Patients with ratios of 2.9 and 1.2 did better (recovered without treatment) than those with rations of 34.6 (unwell 13 days) and 6.9 (still unwell after 11 days). Clinical trials of NAC for prevention and treatment awaited.

The only Input I have: ensure to always use lps from the Same Source with the Same degree of purity....

If you think your selected topic has already been done then why on earth would you want to pursue it? Meta-analysis is a design used to answer a gap in knowledge and if that gap does not exist then why do you still want to pursue a meta-analysis? A new meta-analysis should only be undertaken if a gap in knowledge exists and you believe you have the expertise to undertake a meta-analysis whose purpose is to conclusively answer a critical question.

take a look at Mc Allen RM, AJP, last paper in AJP

THE ANTI-INFLAMMATORY REFLEX ACTION OF THE SPLANCHNIC SYMPATHETIC NERVES IS DISTRIBUTED ACROSS ABDOMINAL ORGANS.

Martelli D, Farmer DG, McKinley MJ, Yao ST, McAllen RM.

Am J Physiol Regul Integr Comp Physiol. 2018 Dec 21. doi: 10.1152/ajpregu.00298.2018. [Epub ahead of print]

PMID: 30576218

Similar articles

This may help. Best. LQ.

@

Dr. Zhang: how did you measure the variables (TTP, arrival time, slopes) in contrasted images using the Mindray M9 machine??

I`m trying to find the control sequences and I`m not able.

If you can help me, it would be great.

It is controversial if controlling fever can affect patients' outcome. Apart from specific subgroups (Neuro, IHD where tachycardia can induce ischemia). Moreover, in sepsis, we monitor response to antimicrobials by monitoring the temperatur. So, and in order to avoid the undesirable NSAIDs, I think paracetamol in general is more than enough.

it can be tried and possibly it will be the future procedure

Little data known about sorbents in HF.

For example: Evaluation of Cross-Linked Polyelectrolyte (CLP) With Placebo in Heart Failure Subjects (STEPWISE).

"CLP-1001 has shown great promise in alleviating the negative impact of fluid overload in heart failure patients as demonstrated in our prior Phase 2a clinical trial. We look forward to reporting data from the STEPWISE trial later this year," said Detlef Albrecht, M.D., Sorbent's President and Chief Executive Officer. "I would like to thank our existing investors for their continued support. This new round of funding and the progress in our lead CLP program take us several steps closer to achieving our goal of bringing a new therapeutic option to advanced congestive heart failure patients."

I have little experience in clinical trials. Results published in N Engl J Med.

CONCLUSIONS

In patients with chronic kidney disease who were receiving RAAS inhibitors and who had hyperkalemia, patiromer treatment was associated with a decrease in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemia.

As Dr Smith has said above,this is a very common issue.

Patients on maintenance haemodialysis,especially those who are oligo-anuric,oscillate between being effectively underfilled post dialysis,and over filled when approaching dialysis,and are very often concurrently hypertensive.

The hypotension following induction of general anaesthesia in that group of patients can be both marked and rapid.

Clearly,volume expansion is not an easy option in anuric haemodialysis patients,and use of vasoconstrictors such as metaraminol or phenylephrine is often required.

Best regards,

Ian

HBOT FOR HEALING OF TISSUE COMPROMISED BY LOW BLOOD FLOWS , IS 

TIME PROVEN & mY EXPERIENCE WITH THIS HAS BEEN VERY GOOD. 

Where there has been compartment syndrome also I feel this therapy will be useful.

Terun,

In an attempt to mitigate the blood sampling stimulus from your study, you may want to place an intravenous catheter prior to your intervention. You will be able to obtain pre-intervention and post intervention blood sampling without the "needle phobia" neuronal input tainting your results since the stimulus will occur prior to your intervention.  

Regards,

Christopher

Hubert,

That is a great question.  There are chambers here in the US that I use that automatically adjusts the compression rate throughout the compression phase of a treatment cycle - the first one-third of the compression phase. The slower compression rate allows the patient to accommodate for initial changes in inner-ear pressure gradually. The chamber then smoothly ramps up the rate to reach the desired Pressure Set. This method allows for maximum patient saturation exposure without exposure to possibly discomforting compression rates. Once the desired pressure set is reached I have not heard of anybody adjusting that until the treatment time is reached.

Hi Karel, it is good question, actually, in this murine model NO is intensively produced due to iNOS expression, and erythrocyte HbNO is following increased NO production, but the effect of increased level of ROS would change the balance and HbNO levels back.  The kinetic model was tested in rat blood (0-72 h. after endotoxin administration):  FR Res Comms 1990 (11 :167-178).  

Hello Mai

Sorry, I don't use Medcalc so can't answer you question directly.  However, a method to incorporate covariates is to run a logistic regression model that includes the biomarkers and covariates then use the output of that model instead of the BM concentrations to plot an ROC and calculate the AUC.

Note:

(i)  Don't put too many variables in the model - normally not more than 1 per 10 (or 15) of your outcome variable (high BP if I understand it correctly).

(ii) consider the alternative approach of a linear regression rather than logistic (or ROC curves).  I suggest this because it seems you have a continuous variable (BP) you want to predict rather than a dichotomous one.

(iii) If you do use logistic regression - consider first making a model with variables known to affect BP.  Then make a new model with the same variables + your BM to see if it makes a difference.  Appropriate stats for this are the IDI & Risk Assessment Plots. (see  my publication for an intro to this)

(iv) Personally I have stopped using the term "statistical significance" and encourage others to do the same.  This is because it is misleading language and p<0.05 is arbitrary and often has little clinical meaning.

All the best

It depends if the patient is mechanically ventilated or spontaneously breathing. Beside the clinical signs of dehydration, leg raise test associated with change in pulse pressure or cardiac output (by CO monitor or echo) is a good test. Most studies define fluid responsiveness as increase in CO/SV by 10-15%.

In mechanically ventilated patients, we use the heart-lung interaction and positive pressure ventilation, either by IVC assessment by echo (collapse more than 12%) or stroke volume variation (LIDCO). PICCO also is of great help.

Fluid responsiveness is a dynamic test and should be repeated through the management till the shock state had been resolved.

Septic cardiomyopathy is well described common phenomenon. It consists the cardiac part of multiple organ dysfunction associated with sepsis. In 1951, Waisbren was the first to describe a subtype of septic patients with hypodynamic circulation (Waisbren BA. AMA Arch Intern Med. 1951;88: 467– 88). This had been confirmed by a pioneer work by Parker et al in 1984 (Parker MM et al. Ann Intern Med. 1984; 100:483– 90). Septic cardiomyopathy can occur in 40-50% of septic shock patients, involving the left as well as the right heart, diastolic and systolic function.

 Many mechanisms had been implicated to explain septic cardiomyopathy. Overt coronary artery disease had been largely excluded by pioneer work since 1980s. In fact, coronary blood flow is increased in sepsis while oxygen extraction is diminished (Cunnion RE el al. Circulation 1986; 73: 637–44). Animal model suggested a circulating myocardial depressant substance (Parrillo JE et al. J Clin Invest. 1985;76:1539-53). Many molecules had been accused (e.g. Endotoxin, IL1, TNF, NO). Other possible mechanisms include myocardial dysfunction, apoptosis, microcirculatory failure.

In general, septic cardiomyopathy remains an interesting area of research and current and future works should increase our understanding of the condition.

Best regards.

There is no proven role of low dose dopamine as renoprotective agents. A mata-analysis  reviewing 21 trials in 970 patients showed no added advantage of low dose dopamine. Instead, higher adverse events were recorded in patients who were give low dose dopamine for renoprotective effect.

Measuring GCS in the sedated population can lead to incorrect SOFA scoring, even in those patients receiving a daily drug "holiday". The lingering effects of sedatives can decrease perceived/measured mentation. So, my answer is, that there is no easy way to address this precisely. We try to assess prior to sedation, when able, then continue with this score until off sedation for an adequate period of time to clear sedative effects.

Does clinical impression and experience matter any more?

I have always used clinical parameters. One simple test is to look at peripheral veins; especially in hands and arms. If they are full, enough fluid has been given. This goes along with other organ perfusion: brain, kidneys and cardiovascular.

I have never been impressed with lactate a  'marker' for sepsis (yes, I know it has been RE-emphasised in new definitions of sepsis). I have seen severely septic patients with various 'intensities of septic shock with normal lactataemia! 

I still believe in looking at the patient and examining them as well as looking (very frequently) at the response to not only fluid therapy but to other supportive measures. Call me OLD FASHIONED - I accept   

Better to read first the book :Gas Dynamics by Liepmann and Roshko. 

we are not using, and i dont feel its wise to start b agonist then get tachycardia and  use the antagonist, if tachycardia is too much then just stop dobutamin and start something else, think norepi.

This is quite debated and confusing to detect living CAPS. According to the citeria of APS, either LA and/or aCL and/or B₂GP1 should be present (12 week apart 2 positive results). Clinically the patient should present thrombotic events (stroke, myocardial infarction, gangrene, pulmonary embolism or DVT) or recurrent miscarriages. However in case of CAPS, kidney and liver function might be disturbed. The major cause of CAPS death is multiple organ failure. APTT might be consistantly significantly high even after regulated warfarin dosages. Please share your experiences as well as this question was posted 1 year back. 

It is a very controversial topic. Infectious complications of the central nervous system (e.g., meningitis, epidural abscess, or others) following regional anesthesia on febrile / septic patients . In 2006, a well written paper by Dr. Horlocker from Mayo Clinic summarized the conflicting results of the studies that examined neurological complications in septic patients undergoing regional anesthesia (Link). Recently and to my best knowledge, my research group have a developed the first meta-analysis of individual participant data (in Peer review yet) on this topic. A total of 234 meningitis cases were found following regional anesthesia, 199 of them were related to spinal anesthesia, of which only 2 cases had previous bacteremia / septicemia. However, it is important to say that in 110 of the 199 cases had not a clear cause of infection (not reported).

In conclusion, actually, there is not a general consensus. As for the actual clinical practice on this topic, sepsis or bacteremia is not still a contraindicated condition for spinal neither epidural anesthesia. 

Of course, it is advised to follow an aseptic technique during the procedure and, from my perspective, wearing surgical masks because the droplets may be a potential source of infection according to our recent work.

Hope this help to answer your interesting question.

Regards

 Dear Hatem,

The septic shock is most likely the result of kidney infection because of obstruction by the stone and diclofenac does not cause septic shock this way.

Diclofenac can influence the outcome from septic shock, by contributing to acute kidney injury in the context of septic shock, or by causing a separate problem such as perforated stomach ulcer which could lead to septic shock, but that is almost certainly not the case here (based on the details you describe).

The 

Dr.Takeuchi,

What is about Cat Scratch Disease (CSD)?

I know about investigations of prof. Soichi Maruyama about wide spread of Bartonellosis among domestic cats in Japan.

Bartonella quintana is agent of infection disease with similar symptoms: “high fever and conscious disturbance”.  Staphylococcus epidermidis in your case can be of agent limphoadenoiditis (superinection). It is not so rare in CSD cases.

Alexander

Dear Sir,

Thank you for your kind response.

I will look at these items with interest.

Best wishes

Jeremy

Troponin might be an indicatior for septic cardiopathy as one puzzlestone in septic multiorganic failure.

Should be considered to study for and should be proposed to e.g. Sepsis Surveillance Compain!

The current reccomendation is to treat patients with refractory septic shock with Hydrocortisone 50mg q6h or 200mg/24h continuously. Refractory shock is not well defined: it is based on Annane's landmark study on corticosteroids in septic shock which showed a mortality benefit- they defined it as persistent shock refractory to vasopressors for 1 hour. Subsequently, the Corticus study did not find benefit to corticosteroid administration in terms of mortality, but patients who responded to steroids, reversed their shock faster. They found no benefit to ACTH stimulation tests in this population, measurement of which was previously the recommendation. These patients were not as sick as Annane's patients. Personally, if  a patient is requiring high dose pressors, or more than one pressor, I consider it refractory, and  I add steroids. If you want to grab a cortisol level prior to treatment, I do that, but its not required. Note that even in the CORTICUS study there was no harm to patients receiving steroids.

You have had the right advice already.

One point: In my experience, if the organism waqs sensitive to antibiotics, giving the starting dose and proceeding immediately to surgery  never resulted in recurrent postoperative infection. Howeverm you must know that I always practised complete debgirement of all infected tissue followed by Bovine pericardial reconstruction as needed.

You do not have right to treat these patients. This situation cannot be solved by the answer to a multiple showiest question. How did you get into that situation

Hi,

very nice reviews from Vinh, Lancet Infect Dis 11; Kuhns, DB, NEJM 2010 and Falcone Curr Opin Infect Dis 12. Watch out mainly from Gram (+) indeed but also mold infections and especially breakthrough fungi since those patients are under long-term antifungals.

See u,

With regard to sTM, one always has to remember that injured hepatocytes are a very important and abundant source of the circulating molecule (see some of reaserch papers from myself). It limits the use of sTM as an endothelial activation/injury marker, especially in sepsis and multiorgan failure where liver is commonly affected.

again, as my forespeakers, i would like to highlight theimportance of s e r i a l pct measurements in the trauma patient. The extent of pct secretion of the first 24 - 48 hr is likely to be related to the extent of trauma itself, as well as to other factors influencing this value, like duration or intesity of surgery. Therefore, obtained pct cut-off values of the before mentioned studies lack external validity. One has to keep in mind that in trauma patients not only septic insults, but also other events (like re-surgery, or newly developed circulatory shock of other than inflammatory causes, just to name two of them) can cause pct elevations, or alter the expected decline of pct. Every single pct value has to be carefully evaluated in the clinical context of every single patient.

Thank you Dr Wacharasint for your answer. Just consider that in septic shock subgroup albumin infusion was associated with better outcome.

Great question!

I believe that there is confusion in the literature between patients who have a primarily neurological disease and those that have a primarily a systemic infection.

The "benefit" of normothermia is based on animal models (of TBI and stroke) and lots of observational clinical studies (again stroke and TBI) … so, manitaning normothermia may be reasonable for critically ill patients with TBI and Stroke, but the evidence is of a low grade as there are no RCTs (1,2).

For sepsis, we published a large observational study (3) that suggests for patients with sepsis, that elevated temperature may be beneficial. Others have found a similar relationship and also that antipretic use may be harmful (4). Additionally a small RCT suggest harm with fever supression (5). This conflicts with Frederique Schortgen's (excellent) RCT (6) … but vasopressor dose and 14-day mortality are not the preferred patient-centred outcomes for critical care trials (90-day is better).

There is unfortunately not enough high quality evidence to guide us at present … my preference is to keep the patient in teh hyperthermic range (between 38 and 39C) whilst on CRRT providing I am happy that the circulation is "managing".

It is interesting to me that my answer differs from most of the other answers. My bias is that we should not interfere too much with what teh body is trying to do … the response to stress or infection has evolved over millions of years and hopefully has been selected because it aids survival.

Our group is doing a bit of work in this field … trying to understand whether fever is beneficial for critically ill patients with sepsis and as a separate question (a much more controversial one) … does normothermia reduce disability and death for patients with stroke and TBI.

I hope this helps … references below.

REFERENCES

1.Saxena M, Andrews PJD, Cheng A. Modest cooling therapies (35 degrees C to 37.5 degrees C) for traumatic brain injury. Cochrane Database of Systematic Reviews. (3):CD006811. PubMed PMID: 18646169.

2. Den Hertog HM, van der Worp HB, Tseng M-C, Dippel DW. Cooling therapy for acute stroke. Cochrane Database of Systematic Reviews. 2009(1):CD001247. PubMed PMID: 19160194.

3. Young P, Saxena MK, Beasley CRW, Bellomo R, Bailey M, Pilcher D, et al. Early peak temperature and mortalityin critically ill patients with or without infection. Intensive Care Med. 2011;38(3):437-44.

4. Lee BH, Inui D, Suh GY, Kim JY, Kwon JY, Park J, et al. Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study. Critical Care. 2012;16(1):R33.

5. Schulman C, Namias N, Doherty J, Manning R, Li P, Alhaddad A, et al. The Effect of Antipyretic Therapy upon Outcomes in Critically Ill Patients: A Randomized, Prospective Study. Surgical Infections. 2005;6(4):369-75.

6. Schortgen F, Clabault K, Katsahian S, Devaquet J, Mercat A, Deye N, et al. Fever control using external cooling in septic shock: a randomized controlled trial. American journal of respiratory and critical care medicine. 2012;185(10):1088-95.

We use predominantly CVVHD in this setting. And following the same evidence as Stephen Lapinsky we prefer citrate, unless systemic heparinisation is indicated for another reason. Historically we avoided citrate in patients with liver dysfunction, but are using it more and more in these patients too, especially if the liver function has "stabilised", i.e. not worsening each day.

One of the first things you need to determine (imo) is where the H2S is coming from. Is it released by s.aureus during fermentation/growth on the tissue? or is its release mediated by the immunesystem/woundhealing process. In the latter case, since LPS and LTA are both recognized by TLRs..my guess is that LTA would also induce H2S release. But i would not be surprised if the H2S is mainly released by s. aureus.

I don't have experience using Niccomo, but I have some using Nicom which is similar. I think that it could be a good monitoring for typically anesthetized patients but not really for septic patients. Indeed, the analysis is based on the amount of fluid in the thoracic cavity, which varies a lot during resuscitation of septic patients. Moreover, I am quite sure that you are inserting arterial and central venous lines to treat your septic patients. So, once you've already inserted those lines, why not use a more invasive monitor like Picco or another thermodilution monitor which is definitely more precise?

To conclude, I think that Nicom or Niccomo are good monitors when you really need a minimally invasive monitor like in the OR.

Dear Rahul,

You have to hope and pray that it is for a given patient very much like what you would do if the patient is seen in ER. However, even 30 min may be too late for other patients. I recall a family where one child had Meningococcal sepsis and was on the intensive care unit and survived after having been brought to ER in shock and we there were at least 5-6 hours when she was confused before falling asleep and another 3 hours before we saw the patient. Patient recovered within a week. On the day, we gave the good news to the mother that we will be moving the child from the ICU to a regular floor, another disaster happened. The mother was walking home with her other child and while crossing the street in the front of the hospital, that healthy child went into a shock and died within an hour despite all efforts. I remember the case well because I was at that time doing my ICU rotation as a resident.

In scientific terms, it all depends on what kind of a septic shock you are dealing with and that will of course depend on the host. If you have an adult with an otherwise healthy immune system, it may be too late because of the severity of the immune reaction that involves not only TLR mechanisms but also the participation of multiple pathways of severe infllammation. The capillary damage and the rate of third spacing may be so fast that fluid resuscitation will simply not work. But if you have an immunocompromised person with lets say leukemia and heavy chemotherapy and severe neutropenia, you may have a little more time because the inflammatory response elements are the chemoresistant innate immune response cells.

And of course you need to look at this in the context of the vasculature. How good are the capillary junctions. How good was the heart and lung function. How many organs are in dysfunction already when you start your intervention.

The take home message: 1. Act and remember, as our ICU attending during my residency would always tell us: "Detail kills". You have to do what you have to do fast and know that you may never be fast enough. 2. Keep your hope and remember pessimism is not something that will help your patient. 3. Remember: Septic shock # Septic shock. The picture varies from patient to patient.

hmmm... the Eli Lily company has removed xigris off the shelves due to safety concern and the so called benefit was likened to compare apple to an orange, as the "benefit" data was concluded by comparing a prospective data on treatment with APC to retrospective data aged years ago without it. Thus one of the BIG conclusion was the mortality benefit was largely drive by the improvement in ICU care in recent years rather than APC itself