Keywords
perioperative nutrition - spine surgery - prealbumin - transthyretin - surgical site
infection
Introduction
Malnutrition has been associated with increased risk of perioperative infection, longer
hospital stays, and worse outcome after surgery in a variety of patient populations.[1]
[2]
[3]
[4]
[5]
[6]
[7] The relationship of nutritional status to outcome has been most extensively investigated
in the gastrointestinal surgery literature, where the recognition that malnutrition
has significant negative effects on surgical outcome has resulted in trials of preoperative
nutritional supplementation (Drover et al, verbal discussion at a department lecture).[2]
[3]
[5]
[6]
[8]
[9]
[10]
[11]
[12]
[13]
[14] Early studies used serum albumin concentration as a gauge of nutritional status,
but this marker has fallen out of favor due to several shortcomings including its
long serum half-life (20 days) and its variability secondary to factors such as hydration
status and renal function.[15]
[16]
[17]
[18] Transthyretin, also known as prealbumin, is a protein produced predominantly by
the liver that has one of the highest proportions of essential-to-nonessential amino
acids of any protein in the body, making it a distinct marker of visceral protein
synthesis.[15]
[19] Furthermore, prealbumin has a short half-life of 1.9 days, making it an early indicator
of changes in nutritional status and thus a preferred marker for studies linking malnutrition
to outcome after surgery.
Although malnutrition is especially prevalent—and problematic—in patients with gastrointestinal
malignancy, poor nutritional status is not limited to these patients. Furthermore,
infectious complications after surgery stand out as a significant, and potentially
avoidable, burden on hospital resources. The development of a surgical site infection,
particularly deep wound infections, after spine surgery has significant consequences
for patients and the health care system at large. Postoperative spinal wound infections
generally lead to longer in-hospital lengths of stay, higher costs, and the potential
for reoperation. Moreover, these complications are known to decrease patient satisfaction
and increase patient morbidity and mortality.[20]
[21]
[22]
[23]
[24]
An audit of surgical site infectious complications occurring after spine surgery performed
at our hospital was undertaken to test the hypothesis that impaired perioperative
nutritional status, as indicated by decreased serum prealbumin level, is associated
with infection after spine surgery. There are limited data in the literature regarding
the use of prealbumin as a marker of nutritional status as it relates to outcomes
following major spinal surgery.
Methods
With approval from the University of Pittsburgh institutional review board (IRB PR008120394),
all patients who developed a wound infection after undergoing spine surgery at UPMC
Presbyterian Hospital between January 2008 and December 2011 were identified by querying
the hospital's Infection Control database. The electronic medical record was reviewed
for each patient, and patient demographics, type of surgery, type of infection, interval
between surgery and the development of infection, treatment, hospital length of stay,
and perioperative serum prealbumin levels were recorded.
Over the 48-month span, > 8,000 spine surgeries were performed; of those, 148 patients
(1.9%) were treated for a postoperative surgical site infection. Perioperative serum
prealbumin levels were available for 84 patients. One patient was excluded because
her infection was related to an intraoperative esophageal injury, leaving 83 patients
in the study group ([Table 1]). Patients' ages ranged from 19 to 85 years (mean: 56 years). Preoperative diagnoses
included symptomatic degenerative lumbar stenosis, tumor, traumatic thoracolumbar
fracture, deformity, and syringomyelia. Sixty-nine patients underwent instrumented
fusion, two patients underwent noninstrumented fusion, 11 patients underwent decompression
alone (for tumor, hematoma, or stenosis) and one patient underwent laminectomy for
placement of a cervical syringopleural shunt. Surgeries spanned 2 to 10 levels (median:
5; interquartile range: 3).
Table 1
Patient characteristics
|
Age, y[a]
|
55.8 (19–85)
|
|
Sex, % female
|
71.4
|
|
Diagnosis, n (%)
|
|
|
Stenosis
|
56 (67.5)
|
|
Trauma
|
8 (9.6)
|
|
Tumor
|
7 (8.4)
|
|
Deformity
|
7 (7.1)
|
|
Hematoma
|
4 (4.8)
|
|
Syringomyelia
|
1 (1.2)
|
|
Spinal level, n (%)
|
|
|
Occipitocervical
Cervical
|
2 (2.4)
17 (20.5)
|
|
Thoracic
|
5 (6.0)
|
|
Thoracolumbar/-pelvic
|
8 (9.6)
|
|
Lumbar
|
51 (61.4)
|
|
Procedure, n (%)
|
|
|
Instrumented fusion
|
69 (83.1)
|
|
Noninstrumented fusion
Decompression alone
|
2 (2.4)
11 (13.3)
|
|
Shunt
|
1 (1.2)
|
|
Number of levels[b]
|
5, 3 (2–10)
|
a Mean (range).
b Median, interquartile range (range).
Prealbumin levels were obtained on readmission to the hospital at the time patients
presented with a wound infection, prior to operative debridement. Nutritional status
was subsequently categorized based on the prealbumin values described by Bernstein
and colleagues.[25] Patients with prealbumin levels < 20 mg/dL were considered malnourished. Patients
were then subcategorized into three groups: mild malnutrition (prealbumin 11–19 mg/dL),
moderate malnutrition (prealbumin 7–10 mg/dL), and severe malnutrition (prealbumin < 7
mg/dL).
Results
Patients presented with a wound infection between 7 and 345 days after surgery (median:
19; interquartile range: 14). The mean age of patients who presented with infection
was 56 years, compared with a mean patient age of 53 years among those patients who
did not develop an infection. Mean initial operative time for patients who presented
with infection was 2.85 hours compared with 2.65 hours among those patients who did
not develop an infection. Eighteen of 83 patients had a comorbid condition associated
with an elevated risk of malnutrition, and these included malignancy with or without
chemotherapy, diabetes mellitus, chronic pulmonary disease, vascular insufficiency,
and rheumatoid arthritis on immunosuppressive medications. All surgical site infections
were deep to the lumbodorsal fascia, and all demonstrated bacterial growth on cultures
obtained from the deep wound tissue. In 12 patients, treatment consisted of a single
operation in which the wound was irrigated, debrided, and closed. In 71 patients,
treatment consisted of serial debridements (range: 2–13) with placement of a negative
pressure wound dressing, followed by definitive wound closure. In four patients, the
wound was allowed to heal by secondary intention with biweekly irrigation and debridement
followed by replacement of a vacuum-assisted closure device. One patient's infection
was treated with placement of a pigtail catheter into a perinephric abscess. Twenty-one
patients underwent removal of instrumentation as part of the infection treatment.
Hospital length of stay was extended by between 5 and 60 days (median: 13; interquartile
range: 16). In all patients, intravenous antibiotic therapy was administered, based
on the specific recommendations of the Infectious Disease service. All of the infections
were successfully eradicated, and all wounds eventually healed. Infection characteristics
are summarized in [Table 2].
Table 2
Infection characteristics
|
Interval to diagnosis of infection, d[a]
|
19, 14 (7–345)
|
|
Incremental hospital length-of-stay, d[a]
|
13, 16 (5–60)
|
|
No. of surgical debridements[a]
|
2.0, 4 (0–13)
|
|
Perioperative nutritional status (prealbumin, mg/dL)[b]
|
|
|
Normal (≥20)
|
1 (1.2)
|
|
Mildly impaired (11–19)
|
26 (31.3)
|
|
Moderately impaired (7–10.9)
|
32 (38.6)
|
|
Severely impaired (< 7)
|
24 (28.9)
|
a Median, interquartile range (range).
b Number (%).
Overall, 82 of the 83 patients had a prealbumin level below the normal range of 20
to 40 mg/dL: 24 patients had a prealbumin < 7 mg/dL; 32 had a prealbumin level of
7 to 10 mg/dL, and 26 patients had a prealbumin level of 11 to 19 mg/dL ([Table 2]). Following their presentation with a deep wound infection and concomitant nutritional
impairment, all patients received some form of nutritional supplementation. Patients
who demonstrated the capacity for being able to supplement their caloric intake by
mouth received protein shakes and nutritional supplements containing Arginaid (Nestle
Health Science, Florham Park, New Jersey, United States) with meals. The remaining
patients underwent placement of a nasoduodenal feeding tube and were administered
tube feeds. Serial prealbumin levels were followed on an outpatient basis, and supplemental
nutrition continued until prealbumin levels normalized. All patients in this study
maintained follow-up, and no patient developed an additional delayed wound infection.
Discussion
The association of postoperative infectious complications with impaired nutritional
status has been previously demonstrated in the gastrointestinal surgery literature,
and malnutrition is increasingly being recognized as a common problem in hospitalized
patients.[1]
[2]
[3]
[4]
[5]
[6]
[7]
[11]
[15]
[26]
[27] However, the link between impaired nutritional status and increased risk for surgical
site infections has been sparsely studied among patients undergoing spine operations.
In a recent study by Schoenfeld et al[28] of > 5,800 spinal fusion patients obtained from the National Surgical Quality Improvement
Program, the authors found that those with a low serum albumin level were at increased
risk of developing a wound infection. Of note, no studies to date have explored the
association between spine surgical site infections and serum prealbumin levels; prealbumin
is a more optimal marker of nutritional status.
This relationship between nutritional status and spine surgical site infection is
especially noteworthy because of the significant implications of this complication
for patients, who often require one or more additional surgeries and potentially require
removal of instrumentation and long-term intravenous antibiotic therapy, and for the
health care system, which must bear the significant additional cost of treating these
complications.[25] Although hospital-wide programs to reduce infection have traditionally focused on
improving antisepsis policies and procedures, comparatively little effort has been
directed toward optimization of patient nutritional status, despite convincing preliminary
data that nutritional status is a modifiable risk factor for postsurgical infection.
Indeed, several trials of nutritional supplementation in the general surgery, gastrointestinal
surgery, cardiothoracic surgery, and head and neck surgery populations have yielded
clinically and statistically significant reductions in infectious complications and
hospital length of stay. Although preoperative nutritional screening is practiced
by some spine surgeons—particularly, in patients undergoing elective deformity surgery—routine
screening is not widely performed.[29] The identification of a serum marker of nutritional status that would allow surgeons
preoperatively to stratify a patient's risk for developing a deep wound infection
after spine surgery has the potential to reduce the incidence of this troublesome
and costly complication of spinal surgery, and it would enable patients and their
surgeons to optimize their nutritional status before and after spine surgery.
Our observation that 99% of patients who developed postoperative deep wound infections
had a prealbumin level consistent with impaired nutritional status is significant
for several reasons. First, although the importance of adequate nutrition for wound
healing has long been appreciated, the association between impaired nutritional status
and wound infection has been understudied in the spinal neurosurgery literature. Second,
if borne out by the results of an ongoing prospective investigation at our institution,
the identification of prealbumin as a strong, reliable predictor of the development
of a surgical site infection after spine surgery will provide spine surgeons with
a screening tool to identify at-risk patients prior to surgery. Ultimately, these
results should empower surgeons, patients, and hospitals to actively improve surgical
outcome through the implementation of simple and inexpensive programs of perioperative
nutritional supplementation.
It is important to note that the current study suffers from several shortcomings.
First, the study was retrospective in design and therefore subject to the typical
sources of confounding and bias associated with retrospective investigations. Furthermore,
prealbumin levels were only obtained in patients who developed a wound infection,
precluding any calculation of the actual risk conferred by low prealbumin. Additionally,
prealbumin levels were not available for all patients who developed a wound infection,
which raises the question of whether malnourished patients who developed an infection
were more likely to have a prealbumin level drawn than were well-nourished patients
who developed an infection.
Finally, our results are also confounded by heterogeneity in the times at which perioperative
prealbumin levels were drawn. This is problematic because prealbumin is generally
felt to behave as a negative acute-phase reactant, with levels decreasing in times
of stress.[15]
[19]
[25]
[30] In the initial phases of the stress response, catabolic processes predominate and
there is a net loss of nitrogen while available amino acids are diverted preferentially
toward the synthesis of positive acute-phase reactants such as C-reactive protein,
complement proteins, and fibrinogen.[15]
[19]
[25]
[30]
[31]
[32]
[33] Prealbumin levels typically reach a nadir within 3 to 5 days after the initiation
of acute injury, coincident with the peak of nitrogen urinary excretion.[30] Prealbumin levels have also been shown generally to decline during the course of
hospitalization due to a variety of factors including nausea, unpalatable food offerings,
and periods of imposed fasting.[7] As a consequence, the prealbumin levels reported in this study, having all been
obtained in the setting of infection and, in some cases, in the setting of recent
surgery, may not provide a true measure of patients' nutritional status due to the
negative effects of the stress response. Of note, the response of prealbumin levels
under conditions of systemic stress is complex and remains incompletely understood,
with some investigators advocating that prealbumin no longer be regarded as a negative
acute-phase reactant but rather as an active participant in the second wave of the
stress response.[30]
Conclusions
Malnutrition has been shown to correlate with risk of infectious complications after
intra-abdominal surgery, and prealbumin is emerging as the preferred marker for measurement
of nutritional status. We have identified a high incidence of impaired nutritional
status, as indicated by decreased prealbumin level, in patients who developed a deep
wound surgical site infection after spine surgery. Prospective evaluation of preoperative
serum prealbumin levels in determining outcome after elective spine surgery will provide
further insights, and a trial of perioperative nutritional supplementation in at-risk
patients is warranted.
