Matt's rotations are going by fast. His first one was at the local hospital. He was able to do rounds in the ICU with the doctors. A few times he was on his own and had to make recomendations to the doctors on treatment plans. He did amazing (although he would never say that to anyone) It's not very often that I get to see the Pharmacist side of my husband. Sometimes when he doesn't know I am at his work I hear him council with a customer, and it makes me realize how much he knows and how smart he is! So while Matt was on rotation the Pharmacist asked him to write a paper that she could give to a Doctor who had talked to a drug rep on this subject. It took him 3 weeks, a lot of stress and reserch, and in the end he did so well the hospital published it in their news letter! Anyway, here is his paper. Good luck trying to understand it, it is in another laugauge called Doctor :o)
Dr. Tiffany M. Hall PharmD. RPh. Editor
Dr. Robin C. Kent PharmD. RPh.
Assistant Editor
PROCALCITONIN
Matthew Walker, Doctor of Pharmacy Student
Over the past few decades studies have been conducted to determine if there is a correlation between bacterial infections and/or sepsis and increased serum levels of procalcitonin (usually >2 ng/ml). Although many reports are promising, after reviewing much of the literature, it would appear that some studies are underpowered and some extrapolate their positive results inappropriately. Larger and better designed studies are needed to conclude the clinical value of the procalcitonin level.
Procalcitonin appears to be an indicator of the likelihood of a bacterial infection in patients. Procalcitonin is a pro-hormone which is cleaved to calcitonin by the C-cells in the thyroid. Procalcitonin is made by non-neuroendocrine parenchymal cells throughout the body (ie: lung, liver, kidney, fat, muscle, stomach) The cause for an increase in this pro-hormone is not clearly understood but has to do with changes in the promoter for the pro-calcitonin gene, responding to bacterial constituents, or by a secondary proinflammatory cytokine stimulus such as tumor necrosis factor-a. (1,2) Another postulated mechanism of action for increased procalcitonin is the inhibition of the final conversion step of procalcitonin to calcitonin due to the presence of cytotoxins and endotoxins released during bacterial infections. (3,4)
Although the postulated mechanisms causing a rise in procalcitonin appear to be directly related to bacterial infections, levels may be elevated in patients for reasons other than infection, such as: inhalational injuries, burn injuries (without infection), noninfectious pneumonitis, pancreatitis (particularly if obstructive in etiology), mechanical trauma, extensive surgery, and heatstroke (5-7). Although some noninfectious conditions cause an increase in procalcitonin, it has been shown that infectious conditions will also cause a rise in procalcitonin levels (8-11). One randomized single blind study involving 243 patients indicates the levels of procalcitonin closely mirrors the extent of bacterial infection and thus decreased the duration of antibiotic use in lower respiratory tract infections (9). Another single blind randomized study included 302 patients admitted for suspected CAP who were split into two groups, a control group and a group that had treatment based on procalcitonin levels. The procalcitonin group was less likely to receive antibiotics, and those that did were on antibiotics for a shorter duration. However hospital stay was similar between the two groups (10). Even with results like these the biggest controversy remains that trials are limited to a small number of people, the definition of infection often varies between studies, and there exists a lack of standardization of lab equipment and levels reported between the studies.
Some studies require proof of infection through cultures; others use diagnosis criteria set up by different medical groups, yet interpreted by the individual physicians in each study. Due to these wide variations, the question remains, was there an active infection and if so did the procalcitonin levels help, or if there was an incorrectly reported infection, did the procalcitonin level get a bad review when it was not properly used. A study that illustrates this point is one using 105 critically ill patients. Criteria for diagnosis was based on three methods: (1) strict diagnosis using only medical criteria, or that same criteria with (2) the addition of procalcitonin levels either between 0.5-1.1ng/ml for one group or (3) over 1.1 ng/ml for the other group(12). The results of the study show a huge overlap between groups and the diagnosis differed between systemic inflammatory response syndrome, sepsis, and severe sepsis, and were only similar in diagnosing septic shock. Due to these variations, the study results are hard to interpret and especially difficult to compare and contrast with one another (12-14).
Another drawback to many studies is the fact that procalcitonin levels, which are considered to be indicative of sepsis (usually >2 ng/ml), are not always accurate. Although many patients that are septic do reach levels over 2ng/ml, there have also been patients with levels less then 2 ng/ml who have been proven to be septic, and people who are healthy who have been found to have procalcitonin levels in the 2 ng/ml range and even higher (15,16). A study that illustrates this is a case control study involving 200 patients. Of these 200 patients, 50 had positive blood cultures while 150 were control patients without infection. Procalcitonin levels were drawn on each patient and levels were found to be between 0.7-2 ng/ml in non-infected patients and between 11.7-42 ng/ml in infected patients. While many studies show those with sepsis have statistically higher procalcitonin levels, there is much overlap of values in patients diagnosed with sepsis. Care must be used in the evaluation of the data as these studies are based on statistical analysis of groups, and not on individual patients.
Some of the studies conducted on the procalcitonin levels differ depending on when the study was conducted, as there is now a 2nd generation test available which is more sensitive and specific, and also on where the test was conducted, as there is only one test approved in the US and multiple tests available elsewhere. Even with all the tests available, there is no assay that detects the full procalcitonin peptide. Instead, the various tests detect different portions of the procalcitonin peptide and thus differ from one another in specificity and sensitivity as well as by what levels are undetectable (17,18). With these differences one may not be able to accurately compare and contrast one study to another, as they may not have interchangeable results.
Summary:
Procalcitonin appears to be a possible indicator of the likelihood of a bacterial infection in patients. Due to the non-standardized methods within the many studies that have been conducted and the elevated nature of procalcitonin seen in situations other than bacterial infections, one cannot solely rely on the procalcitonin levels as a gold standard method of indicating the nature of a patient’s illness. However it would appear that it may be a useful tool along with clinical signs and symptoms and other laboratory data to make a more certain diagnosis of the patient and possibly duration of treatment.
The usefulness of procalcitonin will be better known in the near future. The “PASS” study (procalcitonin and survival study) is a multi-center randomized controlled interventional trial currently in progress consisting of 1000 patients in the ICU(20). This is the first study powered for superiority and non-inferiority to determine if protocols using procalcitonin levels versus standard of care protocols will decrease mortality in the ICU. There has also recently been newer procalcitonin tests available, such as Kryptor, which increase the speed of the results, and greatly improve the sensitivity and specificity of the test. These advances in laboratory testing, along with the PASS study results should better predict the usefulness of this procalcitonin level and its clinical role.
Reference:
1. Domenech VS, Nylen ES, White JC, et al: Calcitonin gene-related peptide expression in sepsis: Postulation of microbial infection-specific response elements within the calcitonin I gene promoter. J Invest Med 2001; 49:514–521
2. Snider RH Jr, Nylen ES, Becker KL: Procalcitonin and its component peptides in systemic inflammation: Immunochemical characterization. J Investig Med 1997; 45:552–560
3. Oczenski W, Fitzgerald RD, Schwarz S. Procalcitonin: a new parameter for the diagnosis of bacterial infection in the peri-operative period. Eur J Anaesthesiol 1998; 15(2):202-209
4. Briel M, Christ-Crain M, Young J, et al: Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: Study protocol for a randomized controlled trial and baseline characteristics of participating general practitioners. BMC Fam Pract 2005; 6:34
5. Ammori BJ, Becker KL, Kite P, et al: Calcitonin precursors: Early markers of gut barrier dysfunction in patients with acute pancreatitis. Pancreas 2003; 27:239–243 6. Nylen ES, O'Neill W, Jordan MH, Snider RH, Moore CF, et al. Serum procalcitonin as an index of inhalation injury in burns. Res. 1992 Sep;24(9):439-43.
7. Meisner M, Tschaikowsky K, Hutzler A, et al: Postoperative plasma concentrations of procalcitonin after different types of surgery. Intensive Care Med 1998; 24:680-684
8. Jereb M, Kotar T: Usefulness of procalcitonin to differentiate typical from atypical community-acquired pneumonia. Wien Klin Wochenschr 2006; 118:170–174
9. Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al: Effect of procalcitonin-guided therapy on antibiotic use and outcome in lower respiratory tract infections: Cluster-randomised single-blinded intervention trial. Lancet 2004; 363:600–607
10. Christ-Crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in community acquired pnewmonia. AM J Respir Crit Care Med. 2006;174 (1):84-93
11. Clec’h C, Feniere F, Karoubi P, et al: Diagnostic and prognostic value of procalcitonin in patients with septic shock. Crit Care Med 2004; 32:1166–1169
12. Giamarellos-Bourboulis EJ, Giannopoulou P, Grecka P, et al: Should procalcitonin be introduced in the diagnostic criteria for the systemic inflammatory response syndrome and sepsis? J Crit Care 2004; 19:152-157.
13. Nathens AB, Marshall JC: Sepsis, SIRS, and MODS: What’s in a name? World J Surg 1996;20:386–391
14. Vincent JL: Dear SIRS, I’m sorry to say that I don’t like you. Crit Care Med 1997;25: 372–374
15. Liaudat S, Dayer E, Praz G, et al: Usefulness of procalcitonin serum level for the diagnosis of bacteremia. Eur J Clin Microbiol Infect Dis 2001; 20:524–527
16. Von Lilenfeld-Toal M, Dietrich MP, Glasmacher A, et al: Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein. EurJ Clin Microbiol Infect Dis 2004; 23:539–544
17. Snider RH Jr, Nylen ES, Becker KL: Procalcitonin and its component peptides in systemic inflammation: Immunochemical characterization. J Investig Med 1997; 45:552–560
18. Simon L, Gauvin F, Amre DK, et al: Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: A systematic review and meta-analysis. Clin Infect Dis 2004; 39:206–217
19. Becker K, Snider R, Nylen E: Procalcitonin assay in systemic inflammation, infection, and
sepsis: Clinical utility and limitations. Critical Care Med. 2008 Mar;36 (3):941-52
20. Jensen J, Lundgren B, et al: The procalcitonin and survival study (PASS). BioMedCentral Infect Dis.2008; 8:91.
Emma on a horse. Every girl there had to have a turn on this one.
Libbie loved all the car rides.
Owen loved the train, but wasn't so sure of the purple guy next to him.
This is Owen showing me that he can keep his mouth closed while swimming. He was very proud!
Libbie so happy to be in the pool. It's a bit foggy because it was so HOT in there. It was 104 that day and the sun shines right in on the pool.
Here are the kids in our hotel room. I think that they would be happy to just go anywhere and stay in a hotel for a few days and do nothing else. They are so cute. Emma told me she loved that I didn't have to make beds everyday, I loved that too!
Here are the kids at Planet Kid. Owen didn't like to walk on this type of floor and just when Matt got him ok with the idea of it his foot fell through and he was not very happy.
Who doesn't jump on beds when they are at a hotel. (We do even if we are at home;O)
Emma hanging around.
Owen loved to play in the ball pit.
Libbie just relaxing.
Noah had a blast, and the kids were all worn out at the end of the day.
We made it through our trip, never getting lost (thankyou to the garmin) doing everything we wanted too. No one got sick, we never went to the ER. We got to see some of Matts family at a picinic and it was so fun to see them. It was the perfect weekend away!
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