| Literature DB >> 33939393 |
Chukwuemeka Mbagwu1, Matthew Sloan, Alexander L Neuwirth, Ryan S Charette, Keith D Baldwin, Atul F Kamath, Bonnie Simpson Mason, Charles L Nelson.
Abstract
INTRODUCTION: The purpose of this systematic review is to identify whether poor nutrition, as defined by the more commonly used markers of low albumin, low transferrin, or low total lymphocyte count (TLC), leads to more postoperative complications. We hypothesized that it may be possible to identify the levels of these laboratory values at which point total joint arthroplasty (TJA) may be ill advised. To this end, we analyzed the available literature regarding links between these three variables on postoperative complications after TJA.Entities:
Mesh:
Substances:
Year: 2020 PMID: 33939393 PMCID: PMC7478613 DOI: 10.5435/JAAOSGlobal-D-19-00057
Source DB: PubMed Journal: J Am Acad Orthop Surg Glob Res Rev ISSN: 2474-7661
Demographics of Albumin Studies
| Author Name | Study Population | Year | Mean Follow-up Time | Study Type | Hypoalbuminemic Cutoff | Normal Albumin Patient (Total) | Low Albumin Patient (Total) |
| Alfargieny et al[ | THA and TKA | 2015 | 6 mo | R | Not given | Not given | 5 |
| Bohl et al[ | THA and TKA | 2016 | 30 d | R | <3.5 g/dL | 47,639 | 1964 |
| Bohl et al[ | THA and TKA | 2016 | 30 d | R | <3.5 g/dL | 3762 | 755 |
| Courtney et al[ | THA and TKA | 2016 | 6 mo | R | <3.5 g/dL | 587 | 83 |
| Cross et al[ | Not applicable (N/A) | 2014 | N/A | N/A | N/A | N/A | N/A |
| Fu et al[ | THA | 2016 | 30 d | R | <3.5 g/dL | 19,465 | 745 |
| Fu et al[ | TKA | 2017 | 30 d | R | <3.5 g/dL | 33,400 | 1400 |
| Gherini et al[ | THA | Not given | Not given | P | Not given | Not given | Not given |
| Greene et al[ | THA and TKA | 1991 | 1 year | R | <3.5 g/dL | 211 | 6 |
| Gunningberg et al[ | THA, TKA, and coronary artery bypass | 2008 | 30 d | P | <35 g/L | 51 | 4 |
| Huang et al[ | THA and TKA | 2013 | 12 mo | P | Albumin <3.5 mg/dL OR transferrin <200 mg/dL | Not given | Not given |
| Kamath et al[ | THA and TKA | 2016 | Not given | P | <3.5 g/dL | 913 | 185 |
| Kamath et al[ | Revision TKA | 2017 | 30 d | R | <3.5 g/dL | 3838 | 713 |
| Kim et al[ | TKA | 2016 | 4.2 y | R | <3.0 g/dL | 839 | 470 |
| Lavernia et al[ | THA and TKA | 1999 | Not given | P | <or = 34 g/L | 97 | 22 |
| Marín et al[ | THA and TKA | 2002 | Not given | P | <3.5 g/dL | 152 | 18 |
| Mednick et al[ | THA | 2014 | 30 d | R | Not given | Not given | Not given |
| Morey et al[ | TKA | 2016 | 1 year | R | <3.5 g/dL | 2956 | 213 |
| Nelson et al[ | TKA | 2015 | 30 d | R | <3.5 g/dL | 35,573 | 1570 |
| Nelson et al[ | THA | 2019 | 30 d | R | <3.5 g/dL | 23,409 | 1177 |
| Nicholson et al[ | THA | 2012 | Not given | R | Albumin <3.5 g/dL AND TLC <1.50 cells/m | 64 | 26 |
| Nussenbaum et al[ | THA and TKA | 2018 | 2 y | R | Not given | Not given | Not given |
| Rai et al[ | THA and TKA | 2002 | Not given | R | Albumin <3.5 g/dL OR serum transferrin <200 mg/dL, OR TLC <1500 cells/mm3 | Not given | Not given |
| Savio et al[ | THA | 1996 | 1.8 y | R | Albumin <3.5 g/dL, then changed to albumin <3.9 g/dL is normal after the researchers analyzed the data | 51 | 35 |
| Walls et al[ | THA | 2015 | 30 d | R | <3.5 g/dL | 23,116 | 1122 |
| Yi et al[ | Revision THA | 2014 | 90 d | R | <3.5 g/dL | Not given | Not given |
N/A = not applicable; P = prospective; R = retrospective; THA = total hip arthroplasty; TKA = total knee arthroplasty; TLC = total lymphocyte count
Table 1 explains the different demographics of each of the articles of albumin, minus the outcomes and conclusions, which are listed in Table 2.
Biostatistical Numbers Used to Decide Albumin RR
| Author | Normal Albumin Total | Normal Albumin Cases | Normal Albumin No cases | Low Albumin Total | Low Albumin Cases | Low Albumin No Cases | Explanation of Where Numbers Come From[ |
| Kim et al[ | 839 | 29 | 810 | 470 | 28 | 442 | AKI |
| Walls et al[ | 23,116 | 250 | 22,866 | 1122 | 33 | 1089 | Any major complication |
| Courtney et al[ | 587 | 48 | 539 | 83 | 23 | 60 | All complications[ |
| Kamath et al[ | 3838 | 1740 | 2098 | 713 | 427 | 286 | Any complication |
| Bohl et al[ | 3353 | 69 | 3284 | 449 | 20 | 429 | PJI after revision for aseptic indication[ |
| Nelson et al[ | 35,573 | 506 | 35,067 | 1570 | 37 | 1533 | Any major complication |
| Kamath et al[ | 913 | 27 | 886 | 185 | 7 | 178 | Unplanned ICU admission |
ICU = intensive care unit; PJI = periprosthetic joint infection; RR = relative risk, AKI = acute kidney injury
Where in the articles the data were retrieved from.
Added all complications in Table 3, which is the addition of all patients from Table 2.
The complication is the number of patients having a PJI after revision for an aseptic indication. Amount of albumin w/aseptic revisions = 3802 in Figure 1, which separates low albumin from norm albumin. The amount of normal albumin and low albumin w/complications is written in the last paragraph of the results section and is graphed out in Figure 3 of Bohl et al.[10]
Summary of Studies Using Transferrin or TLC as a Marker of Malnutrition
| Definition of Nutrition | Definition of Malnutrition | Amount of Studies Showing Significance[ | Total No. of Patients With Notable Results | Complications Which Reached Significance |
| All parameters within normal limits | Low albumin or transferrin or TLC | 135 | 463 | Chronic septic failure and acute PJI complicating aseptic revision arthroplasty |
| Normal transferrin | Low transferrin | 0[ | 3111 | Wound complications[ |
| All parameters within normal limits | Low albumin or transferrin | 1[ | 2161 | LOS, neurovascular, renal, hematoma/seroma, and any complications |
| Normal TLC | Low TLC | 1[ | 101 | Cost/charges, anesthesia time, surgical time, in-hospital costs, and LOS |
| All parameters within normal limits | Low albumin or TLC | 2[ | 3169 | Function score on the American Knee Society range of motion scale and[ |
PJI = periprosthetic joint infection; TLC = total lymphocyte count, LOS = length of stay
The superscript next to the number refers to the article in which the data were extracted in each associated row. It is not an exponent.
The single study showing significance did not list specific P-values, although it stated that a value of less than 0.05 was significant. It demonstrated, using percentages, that a low transferrin level led to an increased OR for wound complications. Although the study does not explicitly state that the data are significant, the words and the phrasing are highly suggestive of this.
Outcomes and Conclusions of Albumin Studies
| Author Name | Outcomes | Conclusions |
| Alfargieny et al[ | SSI | Perioperative albumin was a notable risk factor for SSI |
| Bohl et al[ | 30-day postoperative outcomes—wound dehiscence, deep vein thrombosis, and other | Patients with hypoalbuminemia had a higher risk of SSI, pneumonia, extended length of stay, and readmission |
| Bohl et al[ | Aseptic indications for revision arthroplasty, septic indications for revision arthroplasty, and PJI | Patients with hypoalbuminemia were three times as likely to have septic indication for revision arthroplasty as compared to patients with normal albumin levels. For those with aseptic indications for revision arthroplasty, patients with hypoalbuminemia had a risk of developing a PJI twice as great as those with normal albumin levels. |
| Courtney et al[ | Postoperative complications: cardiac, pulmonary, and other | Hypoalbuminemic patients were more likely to have a postoperative complication. Morbidly obese patients were more likely to be hypoalbuminemic than nonmorbidly obese patients. When comparing hypoalbuminemic morbidly obese patients with hypoalbuminemic nonmorbidly obese patients, no differences were observed in complication rates. When comparing morbidly obese patients with normal albumin to nonmorbidly obese patients, no differences were observed in complication rates. |
| Cross et al[ | N/A | N/A |
| Fu et al[ | Postoperative complications: cardiac (ie, myocardial infarction or cardiac arrest), septic (ie, sepsis or septic shock), and other | Malnutrition incidence increased markedly from obese I to obese III patients and was a stronger and more consistent predictor of complications after THA than was obesity. |
| Fu et al[ | Postoperative complications: wound (ie, superficial infection, deep SSI, organ space surgical site infection, or wound dehiscence) and other | Hypoalbuminemia was a more consistent independent predictor of complications after TKA than was obesity. |
| Gherini et al[ | Delayed wound healing | Only preoperative serum transferrin levels showed notable value in predicting which patients would have delayed wound healing. None of the other serologic variables, including serum albumin and TLC, proved to be a predictor of delayed wound healing. |
| Greene et al[ | Persistent serous drainage and wound dehiscence | Low albumin and low transferrin, independently or concurrently, were associated with more postoperative complications. |
| Gunningberg et al[ | Surgical wound infection | Low preoperative S-albumin was identified as the only notable predictor for surgical wound infection. |
| Huang et al[ | Complications: cardiovascular, neurovascular, and other | The incidence of complications was higher in malnourished patients than in nonmalnourished patients, regardless of whether they were obese. Renal complications were the most common complication experienced by malnourished patients and occurred at markedly higher rates than for nonmalnourished patients. Age was not a notable factor in developing malnutrition, but the incidence increased steadily through age 70. |
| Kamath et al[ | Unplanned postoperative intensive care unit admission | Patients with low albumin had a higher risk of unplanned postoperative intensive care unit admission. |
| Kamath et al[ | Mortality, superficial wound infection, and other | Patients in the low serum albumin group were statistically more likely to develop deep SSI, organ space SSI, and other complications. |
| Kim et al[ | Incidence of acute kidney injury, hospital stay, and overall mortality | Low albumin within two postoperative days was an independent risk factor for acute kidney injury and increased length of hospital stay in patients undergoing TKA. |
| Lavernia et al[ | Complications, resource consumption, length of stay, and number of in-hospital medical or surgical consults obtained | Patients with low albumin levels had higher charges, higher severity of illness, and longer length of stay. |
| Marín et al[ | Delayed wound healing | Preoperative lymphocyte count of less than 1500 cells/mm3 was associated with a three times greater frequency of healing complications, whereas preoperative serum albumin and transferrin levels had no notable predictive value. |
| Mednick et al[ | Readmission | The risk of readmission after THA increased with growing preoperative comorbidity burden. It specifically increased in patients with a body mass index of greater than or equal to 40 kg/m2, a history of corticosteroid use, and low preoperative serum albumin and in patients with postoperative SSI, a thromboembolic event, and sepsis. |
| Morey et al[ | Wound complications (ie, drainage, hemarthrosis, skin necrosis, and dehiscence) or PJI | Findings called into question the values of serum albumin level and TLC as a surrogate of malnutrition for predicting wound complications after TKA. |
| Nelson et al[ | Mortality, superficial wound infection, and other | Morbid obesity was not independently associated with most perioperative complications measured by the ACS-NSQIP and was associated only with increases in progressive renal insufficiency, superficial SSI, and sepsis among the 21 perioperative variables measured. Low serum albumin was associated with increased mortality and multiple additional major perioperative complications after TKA. Low serum albumin, more so than morbid obesity, was associated with major perioperative complications. |
| Nelson et al[ | Major complications, wound infections, and systemic infections | ORs increased or trended higher for all complications for albumin levels under 3.0 g/dL |
| Nicholson et al[ | Length of stay, intraoperative complications, and postoperative complications | The rate of malnourishment was marked higher in patients having trauma-related surgery than in those having elective surgery. Malnourished patients were at greater risk of prolonged hospital stay. |
| Nussenbaum et al[ | SSI, return to operating room, and other | The investigators saw a statistically significant decrease in both SSI and total complications after the implementation of preoperative screening criteria for elective TKA and THA. No single criterion was found to individually predict the complication and infection reductions. |
| Rai et al[ | Wound healing categories: normal/healthy scar after suture removal, delayed wound healing, and infected | Preoperative nutritional status was among several factors governing postoperative wound healing. Preoperative malnourishment as assessed by the low levels of serum albumin, serum transferrin, and TLC did not necessarily lead to delayed wound healing. Although several authors found high incidences of delayed wound healing and wound infection in malnourished patients, there were none in this study. The risk imposed by malnutrition on wound healing can be modified by surgeon-dependent factors. |
| Savio et al[ | Length of stay | Preoperative serum albumin was the only preoperative serum test associated with length of stay. Albumin was inversely related with length of stay. |
| Walls et al[ | Mortality, superficial incisional SSI, and other | Hypoalbuminemia was a notable risk factor for mortality and major morbidity among THA patients, whereas morbid obesity was only associated with an increased risk of superficial SSI. |
| Yi et al[ | Septic revision and aseptic revision | The presence of one or more laboratory parameters suggestive of malnutrition (ie, low albumin, low transferrin, and low lymphocyte count), although common in both normal weight and overweight patients, was independently associated with both chronic PJI and the development of an acute postoperative infection after an aseptic revision arthroplasty. |
ACS-NSQIP = the American College of Surgeons National Surgical Quality Improvement Program; OR = odds ratio; PJI = periprosthetic joint infection; SSI = surgical site infection; THA = total hip arthroplasty; TLC = total lymphocyte count.
Table 2 is a continuation of Table 1 and lists the outcomes measured in and conclusions derived from each of the studies.
RR of Postoperative Complications of Albumin Levels
| Study | RR | Lower Limit CI | Upper Limit CI | % Weight |
| Kim et al[ | 1.724 | 1.038 | 2.861 | 13.05 |
| Walls et al[ | 2.720 | 1.901 | 3.890 | 15.59 |
| Courtney et al[ | 3.389 | 2.181 | 5.266 | 14.17 |
| Kamath et al[ | 1.321 | 1.232 | 1.416 | 19.16 |
| Bohl et al[ | 2.165 | 1.329 | 3.526 | 13.37 |
| Nelson et al[ | 1.657 | 1.191 | 2.304 | 16.06 |
| Kamath et al[ | 1.279 | 0.566 | 2.894 | 8.60 |
| D + L pooled RR[ | 1.933 | 1.401 | 2.665 | 100.00 |
CI = confidence interval; RR = relative risk
Table 3 is a numerical representation of Figure 1.
Pooled RR using DerSimonian and Laird Random effects model.
Figure 1Graph showing the forest plot for the role of malnutrition in albumin articles based on studies with enough subjects. The (1) and (2) next to Kamath were what was used to identify them in the data analysis and does not correlate with the references at the bottom.
Demographics of Transferrin Articles With Enough Subjects to Perform Pooled Analysis
| Author | Study Type | Patient Population | Transferrin Cutoff | Number Low Transferrin | Number Normal Transferrin | Low Transferrin or Albumin | Normal Transferrin and Albumin |
| Roche et al[ | Retrospective | TKA | 200 | 622 | 2339 | N/A | N/A |
| Huang et al[ | Prospective | THA and TKA | 200 | N/A | N/A | 184 | 1977 |
Outcomes and Conclusions of Transferrin Studies
| Authors | Outcomes | Conclusions |
| Roche et al[ | Postoperative infection, wound complications, concomitant infection with wound complications, and infection after wound complications | Patients with lower values of nutritional markers had higher incidences, and hence, odds ratios of complications. |
| Huang et al[ | Multiple complications and length of stay | Malnutrition had higher rates of postoperative complications and length of stay. |
Table 6 is a continuation of Table 5 and describes the outcomes and conclusions derived from each of the studies.
RR of Transferrin as Risk of Postoperative Complications
| Authors | RR | 95% CI Lower Limit | 95% CI Upper Limit | Weighted Percentage |
| Roche et al[ | 1.630 | 1.318 | 2.015 | 52.66 |
| Huang et al[ | 4.076 | 2.555 | 6.501 | 47.34 |
| D + L pooled RR ( | 2.515 | 1.022 | 6.191 | 100.00 |
CI = confidence interval; RR = relative risk
Table 7 is a numerical representation of Figure 2. The information from Figure 2 and Table 7 were derived from the data in Table 8.
Figure 2Graph showing the forest plot of transferrin articles.
Biostatistical Numbers Used to Determine RR of Transferrin
| Author | Normal Transferrin Total | Normal Transferrin Cases | Normal Transferrin No Cases | Low Transferrin | Low Transferrin Cases | Low Transferrin No Cases | Explanation of Where Numbers Come From |
| Roche | 2339 | 240 | 2099 | 622 | 104 | 518 | Postoperative infection |
| Huang | 1977 | 58 | 1919 | 184 | 22 | 162 | Any complication |
RR = relative risk