Summary of Sepsis and Vitamin D
- Sepsis more likely in those with poor immune systems
Infants, elderly, sick, those with low vitamin D
- Severe Sepsis has been associated with low vitamin D in many studies
- Vitamin D treats Sepsis (RCT- 2015, below)
Reduced: ICU by 8 days, Hospital stay by 7 days, and readmission rate to 0%
- Many studies have found that a high level of Vitamin D also prevents Sepsis
VitaminDWiki recommendations for Vitamin D treatment of Sepsis in ICU
- Restore the Vitamin D levels as soon as possible ( Loading dose = Stoss dose = Bolus dose )
Vitamin D levels can be raised very quickly investigation
However, Injection into muscle may provide better response than a tube down the throat
- Speedup the restoration of Vitamin D with sublingual or topical vitamin D
- Follow loading dose with maintenance doses of vitamin D - probably 50,000 IU weekly
Note: Many studies incorrectly had no maintenance dosing, just loading dose
- Consider reducing Sepsis even more by adding: Omega-3 Magnesium Glutamine
Table of contents
- See also VitaminDWiki
- Most Sepsis children also have a chronic disease (both low vitamin D) – Aug 2018
- 200,000 and 400,000 IU of vitamin D reduced septic shock, length of stay - RCT June 2015
- 2.9 X more likely to recover from Septic Shock in 24 hours if have higher level of vitamin D (> 10 ng?) - 2017
- Two Meta-analyses of ICU and Vitamin D - April and May 2017
- High dose + maint. dose Vitamin D reduce mortality – large RCT Amrein 2014
- The only people who died of sepsis in the hospital were vitamin D deficient – April 2017
- Infants with sepsis have very low Vitamin D levels – Aug 2014
- Neonatal Sepsis 4.8 X more likely if poor Vitamin D receptor – June 2018
- Neonates 1.7 X more likely to get Sepsis if low vitamin D, mothers had low levels as well - July 2018
- Additional cost-effective uses of Vitamin D in medical emergencies (beyond Sepsis)
- Sepsis in general (not vitamin D)
- Sepsis overlap with Systemic Inflammatory Response Syndrome
- Sepsis incidence and mortality is higher than many other health problems
- Meta-analysis concludes: Sepsis 1.8 X more likely if low vitamin D - June 2015
- Vitamin D - a new hope for septic shock - July 2013
- Sever sepsis increased 3.5X in a decade
- Sepsis mortality reduced 4X with Intravenous Vitamin C, Thiamine, and hydrocortisone - March 2017 (without any Vitamin D)
- Update on Vitamin cocktail (without Vitamin D) - May 2018
- Sepsis death prevented in 85% by intravenous vitamin C, vitamin B1,and hydrocortisone LEF Sept 2018
- Sepsis best treated by Thiamine (B1) - Vitamin D, Selenium, etc. also considered - literature review July 2018
- Sepsis injection of 300,000 IU of vitamin D helped in a small RCT Feb 2017
- Subtile Signs of Sepsis - Pintrest -2018
- Sepsis Myths and Facts
- Sepsis is 13 X more likely if poor Vitamin D Receptor – April 2017
See Vitamin D Receptor
- Vitamin D for Sepsis prevention – June 2018
- Severe sepsis may be prevented by 400,000 IU of vitamin D – RCT 2023
- Urinary sepsis – a single Vitamin D injection reduced hospital days by 40 percent – RCT April 2018
- Severe Sepsis associated with very low vitamin D – Sept 2016
- Sepsis in first year of life is much more likely if preterm (low Vitamin D) – May 2017
- all items: Low vitamin D due to surgery or trauma
- Google Search for "SEVERE SEPSIS" OR SEPTIC SHOCK" at VitaminDWiki 115 items as of April 2018
- More sepsis deaths in those entering hospital with low vitamin D – Jan 2014
- Vitamin D and infectious diseases like RTI, TB and Sepsis – Nov 2014
- Sepsis mortality cut in half with Omega-3 – RCT Sept 2017
- Sepsis: 4 fewer days in ICU if add Omega-3 – meta-analysis of 12 RCT – June 2017
- Omega-3 reduced cost of Sepsis by 2900 dollars per patient (12 RCT) – April 2018
Personal note by the founder of VitaminDWiki
My 103 year old father-in-law, who got a lot of vitamin D and Omega-3 , was thought to have sepsis.
Doctors gave up on the sepsis diagnosis after his symptoms went away in a day or so.
Children with Chronic Disease Bear the Highest Burden of Pediatric Sepsis
The Journal of Pediatrics, Volume 199, August 2018, Pages 194-199.e1, https://doi.org/10.1016/j.jpeds.2018.03.056
lAndrew J.ProutMD, MPH12 Victor B.TalisaBS13 Joseph A.CarcilloMD2 Florian B.MayrMD, MPH124 Derek C.Angus MD12 Christopher W.SeymourMD12 Chung-Chou H.ChangPhD56SachinYendeMD, MS124VitaminDWiki
7 X more likely to die if have Sepsis & Chronic Disease
To describe the contemporary epidemiology of pediatric sepsis in children with chronic disease, and the contribution of chronic diseases to mortality. We examined the incidence and hospital mortality of pediatric sepsis in a nationally representative sample and described the contribution of chronic diseases to hospital mortality.
We analyzed the 2013 Nationwide Readmissions Database using a retrospective cohort design. We included non-neonatal patients <19 years of age hospitalized with sepsis. We examined patient characteristics, the distribution of chronic disease, and the estimated national incidence, and described hospital mortality. We used mixed effects logistic regression to explore the association between chronic diseases and hospital mortality.
A total of 16 387 admissions, representing 14 243 unique patients, were for sepsis. The national incidence was 0.72 cases per 1000 per year (54 060 cases annually). Most (68.6%) had a chronic disease. The in-hospital mortality was 3.7% overall—0.7% for previously healthy patients and 5.1% for patients with chronic disease. In multivariable analysis,
- cardiac and
- renal disease, and
- solid organ transplantation
were associated with increased in-hospital mortality.
More than 2 of 3 children admitted with sepsis have ≥1 chronic disease and these patients have a higher in-hospital mortality than previously healthy patients. The burden of sepsis in hospitalized children is greatest in pediatric patients with chronic disease.
Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis: A Randomized, Placebo-Controlled Trial.
Critical Care Medicine:, Post Author Corrections: June 17, 2015, doi: 10.1097/CCM.0000000000001148
Quraishi, Sadeq A. MD, MHA, MMSc; De Pascale, Gennaro MD; Needleman, Joseph S. BS, BA; Nakazawa, Harumasa MD, PhD; Kaneki, Masao MD, PhD; Bajwa, Ednan K. MD, MPH; Camargo, Carlos A. Jr MD, DrPH; Bhan, Ishir MD, MPH
Quraishi, Sadeq A., MD SQURAISHI at PARTNERS.ORG
Placebo 200,000 IU 400,000 IU p ICU LOS 12 days 4 days 3 days 0.83 Hospital LOS 21 days 13 days 14 days 0.03 30 day readmission 20% 0% 0% < 0.001 30 day still alive 70% 70% 80% 0.18
Objectives: To compare changes in vitamin D status and cathelicidin (LL-37) levels in septic ICU patients treated with placebo versus cholecalciferol.
Design: Randomized, placebo-controlled, trial.
Setting: Medical and surgical ICUs of a single teaching hospital in Boston, MA.
Patients: Thirty adult ICU patients.
Interventions: Placebo (n = 10) versus 200,000 IU cholecalciferol (n = 10) versus 400,000 IU cholecalciferol (n = 10), within 24 hours of new-onset severe sepsis or septic shock.
Measurements and Main Results: Blood samples were obtained at baseline (day 1) and on days 3, 5, and 7, to assess total 25-hydroxyvitamin D, as well as vitamin D-binding protein and albumin to calculate bioavailable 25-hydroxyvitamin D. Plasma LL-37 and high-sensitivity C-reactive protein levels were also measured. At baseline, median (interquartile range) plasma 25-hydroxyvitamin D was 17 ng/mL (13-22 ng/mL) and peaked by day 5 in both intervention groups.
Groups were compared using Kruskal-Wallis tests. Relative to baseline, on day 5, median change in biomarkers for
200,000 IU cholecalciferol, and
400,000 IU cholecalciferol groups, respectively,
were as follows:
- 1) total 25-hydroxyvitamin D, 3% (-3% to 8%), 49% (30-82%), and 69% (55-106%) (p < 0.001);
- 2) bioavailable 25-hydroxyvitamin D, 4% (-8% to 7%), 45% (40-70%), and 96% (58-136%) (p < 0.01); and
- 3) LL-37: -17% (-9% to -23%), 4% (-10% to 14%), and 30% (23-48%) (p = 0.04).
Change in high-sensitivity C-reactive protein levels did not differ between groups.
A positive correlation was observed between bioavailable 25-hydroxyvitamin D and LL-37 (Spearman [rho] = 0.44; p = 0.03) but not for total 25-hydroxyvitamin D and LL-37.
Conclusions: High-dose cholecalciferol supplementation rapidly and safely improves 25-hydroxyvitamin D and bioavailable 25-hydroxyvitamin D levels in patients with severe sepsis or septic shock. Changes in bioavailable 25-hydroxyvitamin D are associated with concomitant increases in circulating LL-37 levels. Larger trials are needed to verify these findings and to assess whether optimizing vitamin D status improves sepsis-related clinical outcomes.Notes by VitaminDWiki
- Dr. Quraishi has another another Clinical Trial using 400,000 IU followed by 25,000 IU weekly - due 2022
- Dr. Quraishi has co-authored a chapter Vitamin D, Hospital-Acquired Infections and Mortality in Critically Ill Patients: Emerging Evidence
Publisher wants $31 for the chapter, https://doi.org/10.1007/978-3-319-51908-1_15, references, however, are free
Download the PDF from Sci-Hub via VitaminDWiki
- LL-37 is an antimicrobial peptide - click to see full image
- 400,000 IU increases vitamin D levels by >40 ng in healthy individuals in a few days
But Vitamin D levels increased only about 15 ng for those with sepsis
Suspect those with Sepsis need more than 400,000 IU
- Injection should also be considered - as it totally skips over any digestion problems which might be associated with Sepsis
- See also: Overview Loading of vitamin D, which is widely used to improve ICU outcomes
- 18 fewer hospital days if given 500,000 IU of vitamin D while ventilated in ICU – RCT June 2016 in VitaminDWiki
- Vitamin D loading doses reduce ICU mortality by 30 percent – meta-analysis April 2017 in VitaminDWiki
2.9 X more likely to recover from Septic Shock in 24 hours if have higher level of vitamin D (> 10 ng?) - 2017
Effect of Severe Vitamin D Deficiency at Admission on Shock Reversal in Children With Septic Shock.
J Intensive Care Med. 2017 Jan 1:885066617699802. doi: 10.1177/0885066617699802. [Epub ahead of print]
To evaluate the association of severe vitamin D deficiency with clinically important outcomes in children with septic shock.
We enrolled children ≤17 years with septic shock prospectively over a period of 6 months. We estimated 25-hydroxyvitamin D 25 (OH) D levels at admission and 72 hours. Severe deficiency was defined as serum 25 (OH) <10 ng/mL. We performed univariate and multivariate analysis to evaluate association with clinically important outcomes.
Forty-three children were enrolled in the study. The prevalence of severe vitamin D deficiency was 72% and 69% at admission and 72 hours, respectively. On univariate analysis, severe vitamin D deficiency at admission was associated with lower rates of shock reversal, 74% (23) versus 25% (3); relative risk (95% confidence interval CI): 2.9 (1.09-8.08), at 24 hours and greater need for fluid boluses (75 vs 59 mL/kg).
On multivariate analysis, nonresolution of shock at 24 hours was significantly associated with severe vitamin D deficiency after adjusting for other key baseline and clinical variables, adjusted odds ratio (95% CI): 12 (2.01-87.01); 0.01.
The prevalence of severe vitamin D deficiency is high in children with septic shock admitted to pediatric intensive care unit. Severe vitamin D deficiency at admission seems to be associated with lower rates of shock reversal at 24 hours of ICU stay. Our study provides preliminary data for planning interventional studies in children with septic shock and severe vitamin D deficiency.
PMID: 28335672 DOI: 10.1177/0885066617699802 Publisher wants $40 for the PDF, but provides references for free
- Vitamin D loading doses reduce ICU mortality by 30 percent – meta-analysis April 2017
The two studies, which shared in analysis of 5 Randomized Controlled Trials, came up with different conclusions
some of ICU mortality problems were due to sepsis
Both meta-analyses looked at Quraishi 2015 (at the top of this page and Amrein 2014, which follows
Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial.
JAMA. 2014 Oct 15;312(15):1520-30. doi: 10.1001/jama.2014.13204.
Amrein K1, Schnedl C1, Holl A2, Riedl R3, Christopher KB4, Pachler C5, Urbanic Purkart T6, Waltensdorfer A5, Münch A5, Warnkross H1, Stojakovic T7, Bisping E8, Toller W5, Smolle KH9, Berghold A3, Pieber TR1, Dobnig H10.
Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal.
To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs.
DESIGN, SETTING, AND PARTICIPANTS:
A randomized double-blind, placebo-controlled, single-center trial, conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3 (n = 249) or a placebo (n = 243).
Vitamin D3 or placebo was given orally or via nasogastric tube once at a dose of 540,000 IU followed by monthly maintenance doses of 90,000 IU for 5 months.
MAIN OUTCOMES AND MEASURES:
The primary outcome was hospital length of stay. Secondary outcomes included, among others, length of ICU stay, the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7, hospital mortality, and 6-month mortality. A predefined severe vitamin D deficiency (≤12 ng/mL) subgroup analysis was specified before data unblinding and analysis.
A total of 475 patients were included in the final analysis (237 in the vitamin D3 group and 238 in the placebo group). The median (IQR) length of hospital stay was not significantly different between groups (20.1 days [IQR, 11.1-33.3] for vitamin D3 vs 19.3 days [IQR, 11.1-34.9] for placebo; P = .98). Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28.3% [95% CI, 22.6%-34.5%] for vitamin D3 vs 35.3% [95% CI, 29.2%-41.7%] for placebo; hazard ratio [HR], 0.81 [95% CI, 0.58-1.11]; P = .18; 6-month mortality: 35.0% [95% CI, 29.0%-41.5%] for vitamin D3 vs 42.9% [95% CI, 36.5%-49.4%] for placebo; HR, 0.78 [95% CI, 0.58-1.04]; P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D3 vs 19.0 days (IQR, 11.6-33.8) for placebo.
Hospital mortality was significantly lower with 28 deaths among 98 patients (28.6% [95% CI, 19.9%-38.6%]) for vitamin D3 compared with 47 deaths among 102 patients (46.1% [95% CI, 36.2%-56.2%]) for placebo (HR, 0.56 [95% CI, 0.35-0.90], P for interaction = .04), but not 6-month mortality (34.7% [95% CI, 25.4%-45.0%] for vitamin D3 vs 50.0% [95% CI, 39.9%-60.1%] for placebo; HR, 0.60 [95% CI, 0.39-0.93], P for interaction = .12).
CONCLUSIONS AND RELEVANCE:
Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis generating and requires further study.
clinicaltrials.gov Identifier: NCT01130181. PMID: 25268295 DOI: 10.1001/jama.2014.13204
Download the PDF from VitaminDWiki
Correlation of serum vitamin D level with mortality in patients with sepsis
Indian Journal of Critical Care Magazine 2017 Vol 21, # 4, page : 199--204 DOI: 10.4103/ijccm.IJCCM_192_16
Prakash Vipul1, Consul Shuchi2, Agarwal Avinash1, Gutch Manish1, Kumar Sukriti1, Prakash Ved1
1 Department of Medicine, King George's Medical College, Lucknow, Uttar Pradesh, India
2 Department of OBG, King George's Medical College, Lucknow, Uttar Pradesh, India
Hospital Stay (Table 8)
Deficiency Insufficiency Normal <7 days 48 % 18 % 34 % 7-14 days 87 % 7 % 7 % >14 days 73 % 6 % 21 % Died 100 % 0 % 0%
Note by VitaminDWiki: Study does not seem to define the levels for Deficiency, etc.
Background: Sepsis is the leading cause of mortality in the critically ill. Recently, it has been found in many studies that many trace elements and nutrients do have an effect on human body and if supplemented can improve the prognosis in patients with sepsis.
Aim and Objectives: Primary objective: Whether low Vitamin D is associated with mortality. Secondary objective: To find out association of low Vitamin D levels and morbidity in terms of length of hospital and Intensive Care Unit (ICU) stay.
Subjects and Methods: Following ethical approval, consent will be sought from either the patient or assent from a near relative. Successive patients admitted to the medical emergency and ICU at tertiary care health center who fulfill the following criteria for sepsis, within a 24 h time window, were included in the study.
Results: Among 88 patients evaluated in our study 15 patients (18.2%) were found to have adequate Vitamin D levels and seven patients (8%) were found insufficient and rest 52 patients (73.9%) were found deficient in Vitamin D. Age of the patients ranged between 18 and 82 years with mean (±standard deviation) 45.02 ± 17.69 years. Mean Vitamin D level was found significantly higher among patients with positive outcome than those with unfavorable outcome (expiry) (t = 2.075, P = 0.04). On comparison of the length of hospital stay (morbidity) with Vitamin D levels, we found statistically significant inverse relation between Vitamin D levels and length of hospital stay.
Conclusion: Vitamin D deficiency leads to increased risk of mortality in the critically ill along with prolonged hospital stay.
Lower vitamin D levels are associated with increased risk of early-onset neonatal sepsis in term infants
Journal of Perinatology (2015) 35, 39-45;doi:10.1038/jp.2014.146; published online 7 August 2014
M Cetinkaya1, F Cekmez2, G Buyukkale1, T Erener-Ercan1, F Demir1, T Tunc2, FN Aydin3 and G Aydemir2
OBJECTIVE: To evaluate the effect of vitamin D levels on early-onset sepsis (EOS) in term infants.
STUDY DESIGN: Fifty term infants with clinical and laboratory findings of EOS (study group) and 50 healthy infants with no signs of clinical/laboratory infection (control group) were enrolled. Blood was drawn at the time of admission during the first 3 postnatal days of life in both groups for measurement of 25-hydroxyvitamin D (25-OHD) levels.
RESULT: Maternal and neonatal 25-OHD levels (22.2/8.6 ng ml-1, respectively) in the study group were significantly lower than those of the control group (36.2/19 ng ml-1, respectively, P < 0.001). A positive correlation was detected between maternal and neonatal 25-OHD levels. Severe vitamin D deficiency was significantly more common in the sepsis group.
CONCLUSION: Lower maternal and neonatal 25-OHD levels are associated with EOS. These data suggest that adequate vitamin D supplementation during pregnancy may be helpful to prevent EOS in term neonates.
Clipped from PDF
- “ The incidence of neonatal sepsis varies between 1 and 8 neonates per 1000 live births
- Sepsis accounts for more than 25% of neonatal deaths worldwide
Neonates 1.7 X more likely to get Sepsis if low vitamin D, mothers had low levels as well - July 2018
Association of vitamin D deficiency with an increased risk of late-onset neonatal xepsis.
Background Vitamin D deficiency in mothers and neonates is being recognised increasingly as a leading cause of many adverse health effects in the newborn infant, including sepsis.
Methods A prospective observational study was conducted at a tertiary care Paediatric teaching hospital in northern India to assess vitamin D deficiency as a possible risk factor for late-onset sepsis (LOS) in term and late preterm neonates and also to examine the correlation between maternal and infant vitamin D levels during the neonatal period. Late-onset sepsis (LOS) was defined as the development of signs and symptoms of severe sepsis after 72 h of life and a positive sepsis screen. All term and late preterm neonates admitted with LOS between September 2015 and February 2016 who had not been previously admitted for >48 h and had not been prescribed antibiotics or vitamin D were included in the study. Matched controls were recruited from otherwise healthy neonates admitted with physiological hyperbilirubinaemia. Serum 25(OH) vitamin D was assessed in neonates in both groups and their mothers.
Results A total of 421 neonates were admitted to the neonatal intensive care unit during the study period, 120 of whom satisfied the inclusion criteria, and 60 were recruited as cases. Sixty neonates were recruited as controls who were similar in gender, gestational age, age at admission and anthropometry. The study group had significantly lower mean (SD) vitamin D levels [15.37 ng/ml (10.0)] than the control group [21.37 ng/ml (9.53)] (p = 0.001). The odds ratio was 1.7 (95% CI 0.52-5.51) for LOS in vitamin D-deficient neonates. Mothers of septic neonates also had significantly lower mean (SD) vitamin D levels 17.87 (11.89) than the mothers of non-septic neonates 23.65 ng/ml (9.55) (p = 0.004). Maternal vitamin D levels strongly correlated to neonatal vitamin D levels in both groups.
Conclusion Neonates with vitamin D deficiency are at greater risk of LOS than those with sufficient vitamin D levels.
- Heart attack ICU costs cut in half by Vitamin D – Oct 2018
- Trauma with fracture – 2 weeks longer hospital stay if less than 10 ng vitamin D – Jan 2018
- ICU cost reduced by at least 27,000 dollars if get high dose vitamin D in first week - April 2017
- Vitamin D and Glutamine reduced Trauma Center deaths by half – March 2017
- Chance of dying in hospital cut in half by just 10 ng higher level of Vitamin D – April 2016
- Hospital ICU added high dose vitamin D - malpractice lawsuit costs dropped from 26 million dollars to ZERO - Oct 2016
- 18 fewer hospital days if given 500,000 IU of vitamin D while ventilated in ICU – RCT June 2016
- ICU death rate reduced 3X when a single dose of vitamin D changed the PTH – Nov 2015
- Children stayed in ICU 3.5 days longer if low vitamin D – Dec 2015
- Heart Attack ICU costs reduced $37,000 by $20 of Vitamin D – Nov 2015
- Surgical outcomes are better for higher levels of Vitamin D – systematic review May 2015
- Shorter time in ICU if have higher level of vitamin D – April 2012
- Spinal fusion patients often low on vitamin D - Nov 2011
- Staph infection reduced 50 percent when have more than 30 ng of vitamin D – Aug 2011
- Vitamin D reduces sepsis
- MRSA inpatient cost 2X higher if less than 20 ng vitamin D – June 2011
- 540000 IU before ICU raised vitamin D by 25 ng in 2 days – March 2011
- ICU time is 2X more likely to be longer than 2 days if vitamin D less than 20 ng – Mar 2011
- Virtually all veterans in ICU had vitamin D less than 32 ng – Jan 2011
- Patients low on vitamin D stay in hospital longer after thyroid removal – Dec 2010
- HMOs will save millions of dollars with vitamin D
A Silent Killer Slate April 2016
- There is no easy way to diagnose sepsis. The good news is you probably don’t have it, but here’s how to ask your doctor if you’re worried
- Between 16% and 49 % who get Sepsis will die.
- Until recently, the CDC failed to even mention sepsis in it’s A–Z index of medical terms
- Sepsis costs the U.S. more than $20 billion per year
-  Download "Surviving Sepsis 2012" PDF from VitaminDWiki
referenced by Wikipedia
- Septic Shock - Medical dictionary has the following chart
- Developing a New Definition and Assessing New Clinical Criteria for Septic Shock Feb 2017
For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)
The word VITAMIN does not occur once in the following PDF
Download the PDF from VitaminDWiki
The first world Sepsis congress was held Sept 2016
Sepsis is an orphan disease - it affects so many parts of the body that no single medical profession focuses on it
Medicine.Net has a great Sepsis description
Medical Authors: Charles Patrick Davis, MD, PhD, Medical Editor:Melissa Conrad Stöppler, MD
Sepsis (blood poisoning) facts
Sepsis is a potentially life-threatening medical condition that's associated with an infection; the infection's signs and symptoms must fulfill a minimum of two criteria of a systemic inflammatory response syndrome (SIRS).
Blood poisoning is a nonmedical term that usually refers to the medical condition known as sepsis.
The major SIRS criteria are an increased heart rate, fever, and increased respiratory rate; the young and the elderly may show other early signs and symptoms of sepsis sometimes before exhibiting SIRS criteria.
The majority of cases of sepsis are due to bacterial infection.
Sepsis is treated with hospitalization, intravenous antibiotics, and therapy to support any organ dysfunction.
Prevention of infections and early diagnosis and treatment of sepsis are the best ways to prevent sepsis or reduce the problems sepsis causes.
The prognosis depends on the severity of sepsis as well as the underlying health status of the patient; in general, the elderly have the worst prognosis.
What is sepsis?
Sepsis is a potentially dangerous or life-threatening medical condition, found in association with a known or suspected infection (usually caused by but not limited to bacteria) whose signs and symptoms fulfill at least two of the following criteria of a systemic inflammatory response syndrome (SIRS):
- elevated heart rate (tachycardia) >90 beats per minute at rest
- body temperature either high (>100.4 F or 38 C) or low (<96.8 F or 36 C)
- increased respiratory rate of >20 breaths per minute or a reduced PaCO2 (partial pressure of carbon dioxide in arterial blood level)
- abnormal white blood cell count (>12,000 cells/µL or <4,000 cells/µL or >10% bands [an immature type of white blood cell])
Patients who meet the above criteria have sepsis and are also termed septic. These criteria described above were proposed by several medical societies and may continue to be modified by other medical groups. For example, pediatric groups use the same four criteria listed above but modify the values for each to make the SIRS criteria for children. Other groups want to add criteria, but currently this is the most widely accepted definition.
What causes sepsis?
The majority of cases of sepsis are due to bacterial infections, some are due to fungal infections, and very few are due to other causes of infection or agents that may cause SIRS. The infectious agents, usually bacteria, begin infecting almost any organ location or implanted device (for example, skin, lung, gastrointestinal tract, surgical site, intravenous catheter, etc.). The infecting agents or their toxins (or both) then spread directly or indirectly into the bloodstream. This allows them to spread to almost any other organ system. SIRS criteria result as the body tries to counteract the damage done by these blood-borne agents.
Common bacterial causes of sepsis are gram-negative bacilli (for example, E. coli, P. aeruginosa, E. corrodens, and Haemophilus influenzae in neonates). Other bacteria also causing sepsis are S. aureus, Streptococcus species, Enterococcus species and Neisseria; however, there are large numbers of bacterial genera that have been known to cause sepsis. Candida species are some of the most frequent fungi that cause sepsis. In general, a person with sepsis can be contagious, so precautions such as hand washing, sterile gloves, masks, and clothing coverage should be considered depending on the patient's infection source.
What are the risk factors for sepsis?
- The very young and the elderly are at greatest risk
- People in an intensive-care unit
- People with weakened or compromised immune systems
- People with devices such as IV catheters, breathing tubes, or other devices
- People with extensive burns
- People with severe trauma
What is the treatment for sepsis?
In almost every case of sepsis, patients need to be hospitalized, treated with appropriate intravenous antibiotics, and given therapy to support any organ dysfunction. Sepsis can quickly cause organ damage and death; therapy should not be delayed as statistics suggest as high as a 7% mortality increase per hour if antibiotics are delayed in severe sepsis. Most cases of sepsis are treated in an intensive-care unit (ICU) of the hospital.
Physicians agree that the faster the patient with sepsis is diagnosed and treated, the better the prognosis and fewer complications, if any, for the patient.
Sepsis mortality decreased by 15 percent if conventionally treated within 3 hours - May 2017
Time to Treatment and Mortality during Mandated Emergency Care for Sepsis - NEJM
Download the PDF from VitaminDWiki
Significant association between vitamin D deficiency and sepsis: a systematic review and meta-analysis.
BMC Anesthesiol. 2015 Jun 4;15(1):84. doi: 10.1186/s12871-015-0063-3.
Upala S1,2, Sanguankeo A3,4, Permpalung N5.
BACKGROUND: A number of observational studies have found an association between low vitamin D levels and risk of sepsis. We conducted a systematic review and meta-analysis to determine the overall estimate of risk.
METHODS: This was a systematic review and meta-analysis conducted by online searches (CENTRAL, PubMed/MEDLINE, and EMBASE) was registered in PROSPERO (CRD42014014767). Primary outcome was incidence, prevalence, relative risk or odds ratio of having sepsis or bloodstream infection between patients with vitamin D deficiency and controls.
RESULTS: The initial search yielded 647 articles. Twenty-one articles underwent full-length review and data were extracted from 10 observational studies. Pooled odds ratio of sepsis in participants with vitamin D deficiency was 1.78 (95 % confidence interval CI = 1.55 to 2.03, p < 0.01) compared with controls in studies that reported participant numbers and was 1.45 (95 % CI = 1.26 to 1.66, p < 0.01) in studies that reported an adjusted odds ratio of vitamin D deficiency for developing sepsis. Statistical between-study heterogeneity was low (I(2) = 0 % and 5 %, respectively). Standardized mean difference of 25-hydroxyvitamin D levels in patients with sepsis and controls was -0.24 (95 % CI = -0.49 to 0.00, p = 0.05) and lower in the sepsis group compared with non-sepsis or control participants. The statistical between-study heterogeneity (I(2)) was 0 %.
CONCLUSION: Vitamin D deficiency were associated with an increased susceptibility of sepsis.
PMID: 26041306  Download the PDF from VitaminDWiki
Is vitamin D supplementation a new hope for the therapy of the septic shock?
Endocr Regul. 2013 Jul;47(3):133-6.
Yılmaz H, Sahiner E, Darcin T, Celik HT, Bilgic MA, Akcay A.
Vitamin D is mainly known for its traditional role in the bone mineralization and calcium homeostasis. Recent studies have shown that vitamin D receptors (VDR) are present in almost all the tissues and cells in the human body. In addition, several studies have revealed that vitamin D is important in immunomodulation, regulation of inflammation and cytokines, cell proliferation, cell differentiation, apoptosis, angiogenesis, muscle strength, and muscle contraction. Patients with sepsis have high mortality rate and high deficiency in vitamin D. In addition, septic patients have decreased vitamin D binding-protein (DBP) levels which further exacerbate the vitamin D deficiency. The role of vitamin D treatment in sepsis syndrome has been evaluated in animal model of sepsis where 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] administration was associated with improved blood coagulation parameters in sepsis associated with a disseminated intravascular coagulation.
Vitamin D treatment in vitro has also been demonstrated to modulate levels of the systemic inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), as well as inhibit the lipopolysaccharide (LPS)-induced activation and vasodilation of vascular endothelium.
Vitamin D may enhance the induction of the antimicrobial peptides, cathelicidin and b-defensin, which have been described on mucosal and epithelial surfaces acting as the body's first line of defense against viral and bacterial pathogens.
Vitamin D supplementation may divert attention from relatively simple, natural, and low-cost methods of preventing severe sepsis and septic shock.
Further prospective, randomized and controlled clinical trials of adjunctive vitamin D therapy in patients who are vitamin D deficient are needed in the management of human sepsis syndrome.
Sepsis mortality reduced 4X with Intravenous Vitamin C, Thiamine, and hydrocortisone - March 2017 (without any Vitamin D)
- "The global burden of sepsis is estimated as 15 to 19 million cases annually with a mortality rate approaching 60% in low income countries."
- "The hospital mortality was 8.5% (4 of 47) in the treatment group compared to 40.4% (19 of 47) in the control group"
from study: Hydrocortisone, Vitamin C and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study - Dec 2016
Download the PDF from VitaminDWiki
They injected all Sepsis patients for 6 months and compared results from patients in the previous 6 months
Editorial in Chest, online 7 April 2017: How to give vitamin C a cautious but fair chance in severe sepsis
Download the PDF from VitaminDWiki
Study Described in Naturalhealth April 2017
Vitamin C and sepsis: The genie is now out of the bottle May 2017
by Dr. Levi (writen a nice book on Vitamin C) - which is also in naturalhealth
Review of study by Mercola - July 2017 has video interview of the study author
". . .has already made the protocol its standard of care for sepsis. The hospital president is considering making it standard of care in its other 12 hospitals as well."
- Life Extension Magazine Sept 2018- eith on-going Clinical trials for combination Int. Vit C, B1 and hydrocotisone to stop Sepsis
Might Vitamin D be synergistic with this Vitamin C combination?
- Medscape Getting wider test
19 of 47 sepsis patients died previously
4 out 47 who got the treatment died
- "Sevransky's study plans to involve at least 500 and up to 2,000 patients at multiple hospitals for about a year and a half. The plan is to wrap up work in December 2019"
- Beth Israel Deaconess Medical Center study, involves about 200 patients
- "Similar studies are underway in New Jersey, Slovenia, China, Australia, and Qatar"
- Vitamin C "...dose being studied is about 1.5 grams intravenously, every 6 hours for 4 days"
"In a follow-up paper in April, Marik wrote that vitamin C lowers oxidative stress and inflammation, and it helps stop blood vessels from dilating, which helps maintain blood pressure. People who have sepsis often don't have enough vitamins C and B1, and those vitamins appear to combine with the steroid hydrocortisone to boost the effects."
- Many references at the end of the article
Download the PDF from VitaminDWiki
3 clinical trials are underway to confirm
Sepsis best treated by Thiamine (B1) - Vitamin D, Selenium, etc. also considered - literature review July 2018
A review of micronutrients in sepsis: the role of thiamine, l-carnitine, vitamin C, selenium and vitamin D.
Nutr Res Rev. 2018 Jul 9:1-10. doi: 10.1017/S0954422418000124. _available at sci-hub
Belsky JB1, Wira CR1, Jacob V1, Sather JE1, Lee PJ2.
Sepsis is defined as the dysregulated host response to an infection resulting in life-threatening organ dysfunction. The metabolic demand from inefficiencies in anaerobic metabolism, mitochondrial and cellular dysfunction, increased cellular turnover, and free-radical damage result in the increased focus of micronutrients in sepsis as they play a pivotal role in these processes. In the present review, we will evaluate the potential role of micronutrients in sepsis, specifically, thiamine, l-carnitine, vitamin C, Se and vitamin D. Each micronutrient will be reviewed in a similar fashion, discussing its major role in normal physiology, suspected role in sepsis, use as a biomarker, discussion of the major basic science and human studies, and conclusion statement. Based on the current available data, we conclude that thiamine may be considered in all septic patients at risk for thiamine deficiency and l-carnitine and vitamin C to those in septic shock. Clinical trials are currently underway which may provide greater insight into the role of micronutrients in sepsis and validate standard utilisation.
A portion of table from Sci-Hub
Reduced length of stay and deaths - not statistically significant - too small of a trial
[Effect of vitamin D3 on the severity and prognosis of patients with sepsis: a prospective randomized double-blind placebo study]
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2017 Feb;29(2):106-110. doi: 10.3760/cma.j.issn.2095-4352.2017.02.003.
[Article in Chinese]
Ding F1, Zang B, Fu J, Ji K.
To observe the relationship between vitamin D3 and the severity as well as prognosis in patients with sepsis, and to explore whether exogenous vitamin D3 can improve the prognosis in patients with sepsis.
A prospective randomized double-blind placebo study was conducted. Fifty-seven patients with sepsis admitted to intensive care unit (ICU) of Shengjing Hospital Affiliated to China Medical University from March to November in 2015 were enrolled. Twenty patients with systemic inflammatory response syndrome (SIRS) and 20 healthy volunteers with normal physical examination as control were enrolled during the same time. Patients with sepsis were divided into general sepsis group and severe sepsis group (including septic shock) according to the criteria for the diagnosis of severe sepsis and septic shock in 2012. According to the diagnostic criteria established by the American Endocrine Society, and on the basis of 25-hydroxy vitamin D3 [25(OH)D3], the sepsis patients with deficiency [25(OH)D3 20-30 μg/L] or insufficiency [25(OH)D3 < 20 μg/L] of vitamin D were divided into D3 treatment group (supplemented 300 kU vitamin D3) and placebo group (injected 1 mL physiological saline). 28th day was set as the end point, and the patients with sepsis were divided into survival group and death group. The levels of serum 25(OH)D3 in each group were measured by electrochemical luminescence method, and the difference in 25(OH)D3 levels among patients with different severity, gender, and age were recorded. Procalcitonin (PCT), C-reactive protein (CRP), blood routine, liver and kidney function, electrolytes and arterial blood gas analysis, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure score (SOFA), duration of mechanical ventilation, and length of ICU stay of patients with sepsis were observed. Multivariate Cox proportional hazard regression analysis was used to analyze the risk factors of prognosis in patients with sepsis.
(1) In 57 patients with sepsis, there were 15 patients in general sepsis group, and 42 in severe sepsis group; 29 in D3 treatment group, and 28 in the placebo group; 8 patients died within 28 days with mortality rate of 14.04%. (2) The levels of serum 25(OH)D3 in sepsis group and SIRS group were significantly lower than those in healthy control group [μg/L: 3.92 (< 3.00, 11.22), 6.99 (3.51, 9.77) vs. 17.25 (13.48, 22.50), both P < 0.01], but there was no significant difference in the serum 25(OH)D3 level between sepsis group and SIRS group as well as patients with different degrees of sepsis. The serum 25(OH)D3 level in female patients with sepsis (n = 24) was significantly lower than that in male (n = 33), and the difference was statistically significant [μg/L: <3.00 (<3.00, 3.87) vs. 11.96 (5.14, 17.29), Z = -4.020, P = 0.000]. There was no significant difference in serum 25(OH)D3 level between the young (age <60 years old, n = 30) and the old (age ≥ 60 years old, n = 27) patients with sepsis [μg/L: 4.54 (<3.00, 9.88) vs. 3.00 (<3.00, 15.08), Z = -0.601, P = 0.548]. (3) In patients with sepsis, there was no significant difference in the duration of mechanical ventilation [hours: 41.00 (7.50, 82.50) vs. 67.00 (4.75, 127.75)], length of ICU stay (days: 5.48±4.08 vs. 6.68±4.87) and 28-day mortality (10.34% vs. 17.86%) between D3 treatment group and placebo group (all P > 0.05). It was shown by Kaplan-Meier survival curve analysis that there was no significance in 28-day accumulated survived rate between the two groups [log-rank test: χ 2 = 0.222, P = 0.638]. It was shown by multivariate Cox regression analysis that APACHE II score [relative risk (RR) = 8.487, 95% confidence interval (95%CI) = 1.506-47.835, P = 0.015] and 25(OH)D3 < 20 μg/L (RR = 0.088, 95%CI = 0.013-0.592, P = 0.012) were the risk factors of prognosis in patients with sepsis.
The serum 25(OH)D3 level in ICU patients with sepsis was lower than that in healthy people, but there was no significant difference between patients with sepsis and SIRS. The serum 25(OH)D3 level in sepsis patients was related with gender, and the level of the female was lower than that of the male, but was not related with age. Exogenous vitamin D3 supplementation cannot improve the prognosis of ICU patients with sepsis. APACHE II score and 25(OH)D3 < 20 μg/L were risk factors for the prognosis in ICU patients with sepsis.
PMID: 28625255 DOI: 10.3760/cma.j.issn.2095-4352.2017.02.003
- Author was in a Sepsis coma for 3 months
- "Sepsis affects more than 30m people a year worldwide and kills an estimated 6m people, of whom nearly 2m are children."
- "Of those who do survive, 40% will have post-sepsis syndrome, which leaves them with lasting physical and mental symptoms."
- "Surveys suggest that only 40% of people in Australia have heard of sepsis and only one-third of this group are able to identify a single symptom. Figures are even lower in Brazil where only 14% of the public know what it is"