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Perioperative Risk Factors for One-Year Mortality in Patients With Free-Flap Reconstruction Due to Cancer of the Head and Neck

Perioperative Risk Factors for One-Year Mortality in Patients With Free-Flap Reconstruction Due to Cancer of the Head and Neck



Perioperative Risk Factors for One-Year Mortality in Patients With Free-Flap Reconstruction Due to Cancer of the Head and Neck




Journal of Oral and Maxillofacial Surgery, 2021-06-01, Volume 79, Issue 6, Pages 1384.e1-1384.e5, Copyright © 2021 The Authors


Purpose

Head and neck cancer requiring free-flap reconstruction is associated with relatively high mortality. We aimed to evaluate perioperative risk factors for 1-year mortality in this patient group.

Methods

This is a single-center retrospective analysis of 204 patients operated during 2008 to 2018.

Results

A total of 47 (23.0%) patients died within 1 year. In univariate analysis, there were no differences in the intraoperative course between 1-year survivors and nonsurvivors. Among the 1-year nonsurvivors, preoperative albumin level was lower (39 [36 to 43] vs 42 [39 to 44], P = .032) and the Sequential Organ Failure Assessment admission score was higher (4 [3 to 5] vs 3 [2 to 4], P = .003) than those of the 1-year survivors. Among the nonsurvivors, the preoperative and postoperative levels of leukocytes were higher (7.6 [6.7 to 9.5] vs 6.9 [5.5 to 8.4], P = .002; 11.4 [9.0 to 14.2] vs 8.7 [7.2 to 11.3], P < .001). The highest odds ratios for 1-year mortality in multivariate analysis were American Society of Anesthesiologists A classification greater than 2 (3.9 CI 1.4 to 10.5), male gender (4.0 CI 1.5 to 11), and increase in leukocyte count (1.3 CI 1.1 to 1.5).

Conclusions

One-year nonsurvivors had higher American Society of Anesthesiologists classification and were more often men. The postoperative inflammatory markers were higher in nonsurvivors, while the intraoperative course did not have a significant impact on the 1-year mortality.

Free-flap transfer is a standard method in reconstruction of large defects in major head and neck cancer surgery. Head and neck cancer is accompanied with high long-term mortality; 5-year survival is approximately 50 to 60%. In our previous article assessing the long-term outcomes and causes of deaths after free-flap surgery (FFS) for cancer of the head and neck, we found patient-related factors including low body mass index and advanced American Society of Anesthesiologists (ASA) classification as the most significant risk factors for poor long-term mortality. However, intraoperative factors and surgical complications did not have impact on outcome. This indicates that patient-related factors play an important role in unfavorable outcomes.

Previous studies have shown the high rate of complications and poor long-term outcome in this patient group. , The impact of complications on outcomes has also been shown; medical complications in immediate postoperative phase may lead to compromise long-term outcomes including quality-of-life and mortality. Risk factors for medical complications include mostly patient-related factors. However, the risk factors for poor short-term outcome are not well studied. We determined to analyze retrospectively the possible recordable perioperative factors to recognize the possible risk factors for 1-year mortality in the early phase of the patient care.


Methods

This retrospective study was conducted in Oulu University Hospital, and it is a substudy of our previous study analyzing the long-term mortality and causes of deaths in patients operated with FFS due to cancer of the head and neck. The study protocol was accepted by hospital administration (239/2016). Owing to the retrospective study design, no statement from the local ethics committee was obtained.


Patients

This study included 204 patients who underwent head and neck cancer surgery with free-flap reconstruction in Oulu University Hospital in 2008 to 2018. The patients are operated in the head and neck surgery unit by a multidisciplinary surgical team. Immediate postoperative care is routinely provided at the intensive care unit.


Data Extraction

The data extraction is described in our previous article. Preoperative factors including patient demographics, laboratory values, and tumor staging were retrieved from the medical records. The ASA classification was used to estimate preoperative risks, and Charlson comorbidity index was used to determine the severity of chronic diseases. Laboratory values of the first postoperative day and severity of illness scores (Sequential Organ Failure Assessment; Acute Physiology and Chronic Health Evaluation II) on initial postoperative phase were retrieved from electronic patient data management system of the hospital's intensive care unit. The retrieved data consisted of facts obtainable at intensive care unit discharge. The survival data were retrieved from the causes of death registry of Statistics Finland.


Statistical Analysis

Statistical analysis was performed using SPSS software (SPSS for Windows, version 22.0. [IBM Corp., 2013, Armonk, NY, USA]). Proportional data are presented in numbers and percentages, and continuous variables are presented in medians and 25th to 75th percentiles. Continuous variables were tested using nonparametric Mann-Whitney test, and proportional data were tested using Pearson χ 2 test. Logistic regression analysis was used to estimate odds ratios (OR) for factors related to 1-year mortality. All the categorical and continuous variables with univariate significance <0.1 were included into the model. Continuous variables were categorized using local reference values when possible.


Results


Patient Demographics and Preoperative Factors

Of the 204 patients, 47 patients (23.0%) died within 1 year from the operation. Median survival time of the 1-year nonsurvivors was 218 days (119 to 299). A total of 8 patients died within 3 months from the operation and 1 of them within 30 days.

Most of the 1-year nonsurvivors were men (n = 36 (76.6%), P = .004) and were more often recorded as ASA 3 to 4 (n = 38 (80.9%) versus 85 (54.1%), P = .001) compared with the 1-year survivors. Preoperative leukocyte and C-reactive protein (CRP) levels were higher in nonsurvivors than in survivors (7.6 [6.7 to 9.5] x 10 9 /L vs 6.9 [5.5 to 8.4] x 10 9 /L, P = .002 and 16 [12 to 39]mg/L vs 5 [3 to 20] mg/L, P = .013), and the albumin levels were lower (39 [36 to 43] g/L vs 42 [39 to 44]g/L, P = .019). A total of 30 (85.7%) 1-year non-survivors had tumor stage 3 or 4 in contrast to 75 (64.1%) survivors ( P = .015). There were no other differences between survivors and nonsurvivors in patient demographics or preoperative data ( Table 1 .).

Table 1
Patient Demographics and Preoperative Values
1-Yr Survivors
N = 157
1-Yr Nonsurvivors
N = 47
Missing Data (1-Yr survivors/1-Yr Nonsurvivors) P Value
Male gender 83 (52.9) 36 (76.6) .004
Age 65 [57 to 75] 69 [62 to 76] .061
ASA>2 85 (54.1) 38 (80.9) .001
CCI>1 47 (29.9) 20 (42.6) .106
Smoking 64 (40.8) 23 (49.9) .320
Alcohol abuse 49 (31.2) 16 (34.0) .715
Body mass index 24.2 [20.9 to 27.4] 24.4 [20.7 to 26.7] .716
Tumor stage .060
T1 7 (6.0) 1 (2.9) 40/12
T2 35 (29.9) 4 (11.4)
T3 26 (22.2) 14 (40.0)
T4 49 (41.9) 16 (45.7)
Hemoglobin (g/L) 132 [121 to 143] 131 [114 to 146] 16/3 .778
Thrombocytes (10 9 /L) 277 [220 to 330] 279 [224 to 355] 4/0 .615
Leucocytes (10 9 /L) 6.9 [5.5 to 8.4] 7.6 [6.7 to 9.5] 23/4 .002
CRP (mg/L) 5 [3 to 20] 16 [12 to 39] 117/31 .013
Creatinine mmol/L 63 [55 to 71] 67 [49 to 78] 6/1 .790
Albumin g/L 42 [39 to 44] 39 [36 to 43] 29/12 .019
Tumor .742
Tongue 62 (9.7) 15 (31.9)
Maxilla 18 (11.5) 4 (8.5)
Mandible 20 (12.6) 8 (17.0)
Larynx 15 (9.6) 8 (17.0)
Melanoma 12 (7.7) 5 (10.6)
Palatinal 10 (6.4) 3 (6.4)
Buccal mucosa 14 (9.0) 2 (4.3)
Parotic gland 4 (2.6) 2 (4.3)
Lymphoma 1 (0.6) 0 1/0
Abbreviations: ASA, American Society of Anesthesiologists classification; CCI, Charlson Comorbidity Index; CRP, C-reactive protein.

Intraoperative and Postoperative Factors

There were no differences in the intraoperative variables between 1-year survivors and nonsurvivors. The Sequential Organ Failure Assessment scores in immediate postoperative phase were higher in nonsurvivors (4 [3 to 5] vs 3 [2 to 4], P = .003). The first postoperative day leukocytes were higher in nonsurvivors (11.4 vs 8.9 [7.3 to 12.2], P = .001). The increase between preoperative and postoperative leukocyte count was higher in the nonsurvivors (1.8 [0.7 to 3.4] vs 2.4 [1.3 to 5.7], P = .037) ( Table 2 ).

Table 2
Intraoperative and Postoperative Factors
1-Yr Survivors
N = 157
1-Yr Nonsurvivors
N = 47
P Value
Duration of operation (min) 610 [530 to 682] 635 [549 to 707] .821
Intraoperative blood loss (mL) 580 [350 to 950] 600 [370 to 1,040] .318
Blood transfusion 70 (44.6) 25 (53.2) .299
Intraoperative fluid administration (mL) 5,400 [4,400 to 6,900] 5,400 [4,400 to 6,250] .936
Fluid administration per body weight 82.6 [62.5 to 106.3] 78.5 [65.9 to 110.4] .982
Free flap .05
RFA 60 (38.5) 10 (21.7)
ALT 46 (29.5) 23 (50.0)
LD 1 (0.6) 3 (6.5)
Scapula 6 (3.8) 3 (6.5)
Fibula 20 (12.8) 5 (10.9)
Lateral arm 14 (9.0) 0
Other 9 (5.8) 2 (4.3)
SOFA 3 [2 to 4] 4 [3 to 5] .003
APACHE II 12 [10 to 15] 13 [11 to 15] .057
1.POD hemoglobin (g/L) 99 [94 to 107] 98 [93 to 108] .539
1. POD leucocytes (10 9 /L) 8.7 [7.2-11.3] 11.4 [9.0-14.2] <.001
Increase in leucocytes (10 9 /L) 1.8 [0.7-3.4] 2.4 [1.3-5.7] .037
1.POD CRP (mmol/L) 61 [43 to 87] 78 [47 to 111] .044
Increase in CRP mmol/L 55 [32 to 75] 40 [21 to 66] .410
1 POD (creatinine mmol/L) 56 [48 to 68] 55 [49 to 75] .390
ICU LOS (d) 0.9 [0.8 to 1.7] 0.8 [0.7 to 1.1] .184
Abbreviations: ALT, anterolateral thigh; APACHE II, Acute Physiology and Chronic Health Evaluation II; CRP, C-reactive protein; ICU LOS, intensive care unit length of stay; LD, latissimus dorsi; POD, postoperative day; RFA, radial forearm; SOFA, Sequential Organ Failure Assessment.

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