Anemia and red blood cell transfusion practice in prolonged mechanically ventilated patients admitted to a specialized weaning center: an observational study

Background The impact of anemia and red blood cell (RBC) transfusion on weaning from mechanical ventilation is not known. In theory, transfusions could facilitate liberation from the ventilator by improving oxygen transport capacity. In contrast, retrospective studies of critically ill patients showed a positive correlation of transfusions with prolonged mechanical ventilation, increased mortality rates, and increased risk of nosocomial infections, which in turn could adversely affect weaning outcome. Methods Retrospective, observational study on prolonged mechanically ventilated, tracheotomized patients (n = 378), admitted to a national weaning center over a 5 year period. Medical records were reviewed to obtain data on patients’ demographics, comorbidities, blood counts, transfusions, weaning outcome, and nosocomial infections, defined according to the criteria of the U.S. Centers for Disease Control and Prevention. The impact of RBC transfusion on outcome measures was assessed using regression models. Results Ninety-eight percent of all patients showed anemia on admission to the weaning center. Transfused and non-transfused patients differed significantly regarding disease severity and comorbidities. In multivariate analyses, RBC transfusion, but not mean hemoglobin concentration in the course of weaning, was independently correlated with weaning duration (adjusted β 12.386, 95% CI 9.335–15.436; p <  0.001) and hospital length of stay (adjusted β 16.116, 95% CI 8.925–23.306; p <  0.001); there was also a trend toward increased hospital mortality (adjusted odds ratio [OR] 2.050, 95% CI 0.995–4.224; p = 0.052), but there was no independent correlation with weaning outcome or nosocomial infections. In contrast, hemoglobin level on the day of admission to the weaning center was independently associated with hospital mortality (adjusted OR 0.956, 95% CI 0.924–0.989; p = 0.010), appearing significantly elevated at values below 8.5 g/dl (AUC 0.670, 95% CI 0.593–0.747; p <  0.001). Conclusions A high percentage of prolonged mechanically ventilated patients showed anemia on admission to the weaning center. RBC transfusion was independently correlated with worse outcomes. Since transfused patients differed significantly regarding their clinical characteristics and comorbidities, RBC transfusion might be an indicator of disease severity rather than directly impacting patient prognosis.

This was done because there are frequently large fluid shifts in the first two weeks upon admission, as a result of a negative fluid balance in patients which are overhydrated when transferred from the intensive care unit to the weaning center.
GFR values calculated from creatinine trends that met the criteria of acute renal failure according to Acute Kidney Injury Network (AKIN) criteria [5] during the first 15 days after admission were excluded.

Cardiac disease
Patients` medical records were screened for documented coronary artery disease (diagnosis exclusively based on previous left-heart catheterization) and systolic left ventricular dysfunction (based on a recent echocardiographic examination not more than six months before).

Diabetes mellitus
DM was assessed based on patients` medical records.

Neuromuscular disease
Patients` medical records were screened for documented Parkinson`s disease, multiple sclerosis, myasthenia gravis, myotonic dystrophy, amyotrophic lateral sclerosis, and other types of neuromuscular disease.

Malignancy
Patients` medical records were screened for documented active malignant disease present at the time of treatment.

Immunosuppression
Patients` medical records were screened for documented therapy with glucocorticoids (equivalent to prednisolone ≥ 20 mg per day for more than two weeks) during the course of weaning, chemotherapy or therapy with immunosuppressants not more than three months before, organ transplant, human immunodeficiency virus (HIV) infection category c/stage 3, splenectomy, and active hematologic malignancies.

Definitions of weaning outcome measures
Weaning failure Failure was defined as Category 3c according to the German guideline on prolonged weaning [6], either transition to invasive home ventilation or death on ventilation during the treatment period.

Weaning duration
Time from admission to the weaning center to the point at which weaning was completed.
For Category 3a, equal to the time of the last mechanical ventilation episode, followed by permanent spontaneous breathing up to discharge from the weaning unit.
For Category 3b, equal to the time to transition to non-invasive home ventilation. This is not always the same as the time to extubation/decannulation. If decannulation has been delayed for other medical reasons, such as repeated bronchoscopic interventions for resection of subglottic tracheal stenosis prior to decannulation, then the time was chosen as the end of the weaning process, from which, due to the ventilatory capacity, a switch to NIV was considered.
For Category 3c, equal to the time to transition to invasive home ventilation (this was at the discretion of the treating physician) or death on ventilation during the treatment period.

Hospital lenght of stay
Time between admission to the weaning center and discharge from the hospital.

Hospital mortality
Proportion of patients deceased during their hospital stay.

Criteria for nosocomial infections (CDC) [7]
Hospital Acquired Pneumonia With common bacterial or filamentous fungal pathogens and specific lab findings VAP Pneumonia in patients who had a device to assist or control respiration continuously through a tracheostomy or by endotracheal intubation within the 48-hour period before the onset of infection, inclusive of the weaning period Patient with/without underlying diseases has 2/1 or more serial x-rays with one of the following: -New or progressive and persistent infiltrate -

AND
Urine culture with ≥ 10 3 but < 10 5 colonies/mL of no more than two species of microorganisms AND At least one of the following: -Positive dipstick for leukocyte esterase and/or nitrate -Pyuria (urine specimen with ≥ 10 WBC/mm 3 or ≥ 3 WBC/high-power field of unspun urine) - Organisms seen on Gram`s stain of unspun urine

Other infections of the urinary tract
Kidney, ureter, bladder, urethra, or tissue surrounding the retroperitoneal or perinephric space At least one of the following: 1) Patient has organisms isolated from culture of fluid (other than urine) or tissue from affected site. 2) Patient has an abscess or other evidence of infection seen on direct examination, during a surgical operation, or during a histopathologic examination 3) Patient has at least two of the following signs or symptoms with no other recognized cause: fever (> 38°C), localized pain, or localized tenderness at involved site AND at least one of the following: o Purulent drainage from affected site o Organisms cultured from blood that are compatible with suspected site of infection o Radiographic evidence of infection (e.g., abnormal ultrasound, CT-scan, MRI)

Laboratory-confirmed BSI (primary sepsis)
Clinical Laboratory-confirmed bloodstream infection in a patient without an evident focus 1) Patient has a pathogen cultured from one or more blood cultures 2) Patient has at least one of the following symptoms (fever > 38°C, shivering, hypotonia) AND has a recognized pathogen (defined as a microorganism not usually regarded as a common skin contaminant, i.e., diphtheroids, Bacillus species, Propionibacterium species, coagulasenegative staphylococci, or micrococci) cultured from at least 2 blood cultures drawn on separate occasions

Secondary peritonitis
Clinical setting Patients presenting with an infection of the peritoneal space following perforation, abscess formation, ischemic necrosis, or penetrating injury of the intra-abdominal contents At least two of the following signs or symptoms with no other recognized cause: Abdominal pain in more than 1 quadrant (not localized) -Ileus - Feeding intolerance

AND
Isolation of one or more microbial pathogens found in the peritoneum or the blood 24 hrs after a gastrointestinal perforation of the stomach, esophagus or duodenum, or any perforation of the small bowel distal to the ligament of Treitz

Endocarditis
Clinical setting Patients presenting with SIRS/sepsis without an evident clinical focus, or with persistent SIRS/sepsis despite adequate therapy for any suspected alternative source Endocarditis of a natural or prosthetic heart valve must meet at least one of the following criteria: -Patient has organisms cultured from valve or vegetation -Patient has 2 or more of the following signs or symptoms with no other recognized cause: fever (> 38°C), new or changing murmur, embolic phenomena, skin manifestations (i.e., petechiae, splinter hemorrhages, painful subcutaneous nodules), congestive heart failure, or cardiac conduction abnormality

AND
At least one of the following: -Organisms cultured from 2 or more blood cultures -Organisms seen on Gram's stain of valve when culture is negative or not done -Valvular vegetation seen during a surgical operation or autopsy -Positive antigen test on blood or urine (eg, H influenzae, S pneumoniae, N meningitidis, or Group B Streptococcus) -

AND
If diagnosis is made ante mortem, physician institutes appropriate antimicrobial therapy

Gastroenteritis
Gastroenteritis must meet at least one of the following criteria: 1) Patient has an acute onset of diarrhea (liquid stools for more than 12 hours) with or without vomiting or fever (> 38°C) and no likely noninfectious cause (e.g., diagnostic tests, therapeutic regimen other than antimicrobial agents, acute exacerbation of a chronic condition, or psychologic stress) 2) Patient has at least two of the following signs or symptoms with no other recognized cause: nausea, vomiting, abdominal pain, fever (> 38°C), or headache and at least 1 of the following: o An enteric pathogen is cultured from stool or rectal swab o An enteric pathogen is detected by routine or electron microscopy o An enteric pathogen is detected by antigen or antibody assay on blood or feces o Evidence of an enteric pathogen is detected by cytopathic changes in tissue culture (toxin assay) o Diagnostic single antibody titer (IgM) or 4fold increase in paired sera (IgG) for pathogen