Postoperative Acute Phase Response Research Articles

Does adding corticosteroids to periarticular injection affect the postoperative acute phase response after total knee arthroplasty?

BackgroundPeriarticular injection (PAI) can reduce pain and improve early outcomes following total knee arthroplasty (TKA). Although corticosteroid PAI has been reported to be safe and effective, investigations on the postoperative acute phase response (APR) are scarce. MethodsThis retrospective cohort study with propensity score matching investigated two groups of patients after TKA: the steroid group (n = 50) received an intraoperative corticosteroid PAI (methylprednisolone 40 mg); the non-steroid group (n = 50) did not receive the corticosteroid. To evaluate the APR, C-reactive protein (CRP) levels and erythrocyte sedimentation rates (ESR) were determined preoperatively and on postoperative day (POD) 2, 4, 6, 14, and 28. A visual analogue scale (VAS) was used to measure pain on the night of surgery and on POD 1, 2, 4, and 6. Maximal flexion at discharge (POD 7), morphine equivalent dose (MED), and complications were also evaluated. ResultsThe steroid group showed significantly lower CRP levels on POD 2 (P < .05) and POD 4 (P < .05) but a higher CRP level on POD 6 (P < .05). However, ESR levels did not differ between the two groups in all measurements. Peak values in CRP and ESR in the steroid group (POD 4 and 6) appeared two days later compared with the non-steroid group (POD 2 and 4). The VAS pain score was significantly lower in the steroid group on POD 2 (P < .05). Maximal flexion on discharge, MED and complication rate were similar in the two groups. ConclusionsAdding a corticosteroid to the PAI following TKA attenuated the APR, and also provided significant pain relief.

Sleeve Gastrectomy With or Without a Multimodal Perioperative Care. A Randomized Pilot Study.

Multimodal protocols may enhance postoperative recovery. The aim of this study was to evaluate the influence of a multimodal protocol in the clinical results, insulin resistance, and inflammatory response to trauma in morbidly obese patients undergoing sleeve gastrectomy. The population of the study consisted of morbidly obese patients, who were operated using sleeve gastrectomy, from Cuiaba, MT, Brazil, between April and October 2012. Twenty patients were divided into two groups whom received either traditional preoperative care or treatment following the Acerto (accelerating the total recovery of patients in the postoperative period) protocol. The study examined inflammatory response and insulin resistance by measuring levels of glucose, insulin, Homa-IR, reactive C protein, albumin, prealbumin, alpha 1 acid glycoprotein, interleukin 6, and glycosylated hemoglobin. In addition, the study investigated hydration levels, nausea and vomiting, hypertension, and length of hospital stay. Patients who followed the Acerto protocol showed no postoperative hypertensive crises (p = 0.03), and 30 % less vomiting (p = 0.35), and showed significant reductions in length of hospital stay, on average of 3 days versus 2 days (p = 0.02). There were not significant statistical differences between the two groups with respect to inflammatory response and insulin resistance (p > 0.05). This pilot study suggests that the prescription of the Acerto multimodal protocol for morbidly obese patients undergoing sleeve gastrectomy was safe, reduced the rate hypertensive complications, and the length of both ICU and hospital postoperative stay. However, there was no improvement in postoperative insulin resistance or inflammatory acute phase response.

Effects of preoperative feeding with a whey protein plus carbohydrate drink on the acute phase response and insulin resistance. A randomized trial

BackgroundProlonged preoperative fasting increases insulin resistance and current evidence recommends carbohydrate (CHO) drinks 2 hours before surgery. Our hypothesis is that the addition of whey protein to a CHO-based drink not only reduces the inflammatory response but also diminish insulin resistance.MethodsSeventeen patients scheduled to cholecystectomy or inguinal herniorraphy were randomized and given 474 ml and 237 ml of water (CO group) or a drink containing CHO and milk whey protein (CHO-P group) respectively, 6 and 3 hours before operation. Blood samples were collected before surgery and 24 hours afterwards for biochemical assays. The endpoints of the study were the insulin resistance (IR), the prognostic inflammatory and nutritional index (PINI) and the C-reactive protein (CRP)/albumin ratio. A 5% level for significance was established.ResultsThere were no anesthetic or postoperative complications. The post-operative IR was lower in the CHO-P group when compared with the CO group (2.75 ± 0.72 vs 5.74 ± 1.16; p = 0.03). There was no difference between the two groups in relation to the PINI. The CHO-P group showed a decrease in the both CRP elevation and CRP/albumin ratio (p < 0.05). The proportion of patients who showed CRP/albumin ratio considered normal was significantly greater (p < 0.05) in the CHO-P group (87.5%) than in the CO group (33.3%).ConclusionsShortening the pre-operative fasting using CHO and whey protein is safe and reduces insulin resistance and postoperative acute phase response in elective moderate operations.Trial registrationClinicalTrail.gov NCT01354249

Dietary Restriction Modifies Certain Aspects of the Postoperative Acute Phase Response

Lifespan extension is achieved through long-term application of dietary restriction (DR), and benefits of short-term dietary restriction on acute stress and inflammation have been observed. So far, the effects of short-term DR in humans are relatively unknown. We hypothesized that short-term DR in humans reduces the acute phase response following a well defined surgical trauma. Thirty live kidney donors were randomized between 30% preoperative dietary restriction followed by 1 d of fasting (n=17) or a 4 d ad libitum regimen (n=13) prior to surgery. Leukocyte subsets and numbers and serum cytokine levels were determined. Whole blood was stimulated with lipopolysaccharide (LPS) and cytokine production was determined. A clear trend towards lower numbers of postoperative circulating leukocytes was observed in the DR group. IL-8 serum levels were significantly higher in the DR group over the first 6 postoperative d (P=0.018). After LPS stimulation, significantly less TNF-α (P=0.001) was produced by blood obtained postoperatively compared with preoperative blood from the DR group. This was not observed in the control group. A relatively short preoperative dietary restriction regimen was able to modify certain aspects of the postoperative acute phase response. These data warrant further studies into the dietary conditions that improve stress resistance in humans. (Dutch Trial Registry number: NTR1875).

Acute Phase Response to Surgery of Varying Intensity in Horses: A Preliminary Study

To evaluate the postoperative inflammatory response of horses to elective surgery of varying intensity. Prospective longitudinal study. Horses referred to 2 hospitals for either arthroscopic removal of a unilateral osteochondritic lesion in the tibiotarsal joint (minimal surgical trauma, n=11), correction of recurrent laryngeal neuropathy by laryngoplasty and ventriculectomy (intermediate surgical trauma, n=10) or removal of an ovarian tumor by laparotomy (major surgical trauma, n=5). Horses had a thorough clinical examination every day. White blood cell (WBC) counts and concentrations of serum amyloid A (SAA), fibrinogen, and iron were assessed in blood samples obtained before, and 1-3, 5, 7, 9, and 11 days after surgery. Differences in levels of the inflammatory markers between the 3 surgical groups were analyzed using repeated measures ANOVA. Postoperative concentrations of SAA and fibrinogen were significantly higher in horses that had laparotomy and ovariectomy than in horses that had laryngoplasty and ventriculectomy, or arthroscopy. Iron concentrations decreased to lower levels after intermediate and major surgical trauma than after small surgical trauma. WBC count did not differ between the 3 groups. Levels of SAA, fibrinogen, and iron reflected the intensity of the surgical trauma, whereas WBC count did not. Postoperative measurements of SAA, fibrinogen, and iron may be useful for comparing surgical trauma associated with new and established surgical techniques. Moreover, knowledge of the normal postoperative acute phase response is essential, if acute phase reactants are to be used for monitoring occurrence of postoperative infections.

VASOPRESSORS IN CARDIAC SURGERY: THE ROLE OF THE ADRENAL GLAND

PURPOSE: Serum total cortisol level has been used for the diagnosis of adrenal insufficiency. However, more than 90% of circulating cortisol is protein-bound and this can affect the assessment of adrenal gland reserve in cardiac surgery patients, because the binding protein levels fall substantially during the postoperative acute phase response. To evaluate cortisol levels and their relationship to albumin levels in the context of severe stress and the acute phase response in patients undergoing cardiac surgery and to assess if the cortisol/albumin (C/A) ratio can be used to predict the need for vasopressors postoperatively.

Clinical influence of vagotomy on postoperative acute phase response

Although there is increasing evidence suggesting that the vagus nerve functions as a connector between the nervous and immune systems in animals, little is known about the role of the vagus nerve in postoperative acute phase response in humans. The extent of fever and acute phase protein response and the production of inflammatory cytokine during the early postoperative period were compared among the patients who had undergone total gastrectomy including truncal vagotomy (n = 13), those having distal gastrectomy with division of vagal branches (n = 14), and the patients with vagal nerve preserving gastrectomy (n = 12). There was no significant difference in serum levels of C-reactive protein, alpha-1-antirypsin, and interleukin-6 among the three groups. Also, postoperative maximum body temperature was similar. Vagotomy did not influence acute phase response after gastric cancer surgery. A multipathway mechanism for acute phase response including the induction of fever is suggested.

Variable Mannose-Binding Lectin Expression during Postoperative Acute-Phase Response

Low plasma concentrations and genetic polymorphisms of mannan-binding lectin (MBL) have been associated with infectious disease complications during various conditions. The present study examined the nature and expression of MBL deficiency during a surgery-induced acute-phase response. Blood was sampled from 20 consecutive patients before and 1, 3, 5, 7, and 10 days and 6 weeks after a uniform abdominal operation (transhiatal esophagectomy). Plasma concentrations of MBL, C-reactive protein (CRP), and secretory phospholipase A2 (sPLA2) were measured. Patients were classified as low- or high-level MBL producers by their preoperative concentration (<0.5 or > or = 0.5 micrograms/mL), and were cross-verified for actual MBL deficiency by nucleotide sequencing of both the MBL promoter and exon-1 alleles. Baseline plasma MBL concentrations correlated with maximal postoperative plasma concentrations (r = 0.88; p < 0.0001). This was not found for CRP and sPLA2 (r = 0.19 and r = 0.08, respectively). Alleles responsible for structural MBL variants were detected in 40% of patients and were associated with significantly reduced MBL concentrations (p = 0.005). The baseline cut-off value in plasma of 0.5 micrograms/mL clearly identified individuals with variant exon-1 alleles (sensitivity 100%, specificity 83%). Baseline MBL plasma concentrations are predictive of MBL expression during the acute-phase response. A baseline cut-off value of 0.5 micrograms/mL can be used to identify patients with variants in the exon-1 region of the MBL gene without the need for nucleotide sequencing. Clinical studies may use this easy and quick method to identify MBL deficient patients preoperatively, as they are conditionally at risk for infectious complications.

Reduced complement activation during cardiopulmonary bypass does not affect the postoperative acute phase response

In the present study the relationship was evaluated between perioperative inflammation and the postoperative acute phase response in patients undergoing elective coronary artery bypass grafting (CABG) assisted by cardiopulmonary bypass (CPB). CPB circuits contained either non-coated- (UMS), Carmeda- (BPS) or Trillium-coated oxygenators (BAS). Prospectively, 71 CABG patients were randomly allocated to one of the oxygenator groups (UMS: n=25, BPS: n=25 and BAS: n=21). Terminal complement complexes (TCC) and elastase were determined in plasma samples collected before, during and after bypass. Secretory phospholipase A2 (sPLA2) and C-reactive protein (CRP) were determined before and after bypass. Demographic, CPB and clinical outcome data were similar for the three groups. TCC and elastase increased during CPB, and decreased thereafter. Significant differences between the groups were present in the levels of TCC at the end of CPB (P=0.002) and at the first (P=0.012) and second (P<0.001) postoperative days, the BPS and BAS groups having reduced levels of TCC compared to the UMS group. Also elastase concentrations differed significantly between the groups at the end of CPB (P<0.001). The postoperative sPLA2 and CRP levels increased in all three groups on the first and second postoperative days, but no significant differences were present between the groups. Material-induced reduction of the inflammatory response during CPB does not affect the postoperative acute phase response. Thus, in CABG patients this response seems relatively unaffected by the composition and/or biocompatibility of the modern CPB circuit and rather to be evoked by surgical trauma, anesthetics and organ perfusion.

Free Serum Cortisol during the Postoperative Acute Phase Response Determined by Equilibrium Dialysis Liquid Chromatography-Tandem Mass Spectrometry

In severely ill patients low concentrations of the corticosteroid binding globulin are typically found; the aim of this study was to quantify directly free bioactive cortisol concentrations in the sera of postoperative cardiosurgical patients. Serum samples of 12 consecutive patients undergoing aortocoronary bypass surgery taken preoperatively and on the postoperative days 1 to 4 were analyzed. Total serum cortisol was quantified using liquid chromatography-tandem mass spectrometry with an on-line sample extraction system and tri-deuterated cortisol as the internal standard, and free serum cortisol was measured after over-night equilibrium dialysis. Whereas on the first postoperative day, the median total serum cortisol concentration was approximately two-fold increased compared to preoperative samples (preoperatively, 245 nmol/l (interquartile range (IQR) 203-293 nmol/l); first postoperative day, 512 nmol/l (IQR 410-611 nmol/l)), median dialyzable free cortisol concentration was almost seven-fold increased (preoperatively, 14.2 nmol/l (IOR 10.9-20.7 nmol/l); first postoperative day, 98.3 nmol/l (IQR 81.3-134 nmol/l)). On the fourth postoperative day, median free cortisol was still significantly increased compared to baseline sampling (p < 0.05), whereas median total cortisol was not. A median of 5.7% (IQR 5.4-7.0%) of total cortisol was found as free cortisol on the preoperative day, 21.2% (IQR 18.9-23.5%) on the first postoperative day and 10.5% (IQR 9.8-14.0%) on the fourth postoperative day. It is concluded that during the postoperative period the free-to-bound ratio of cortisol is highly variable and that during the acute phase response direct quantification of free bioactive cortisol concentrations seems to be biologically more appropriate than the measurement of total cortisol concentrations.

Does age affect liver function and the hepatic acute phase response after major abdominal surgery?

The liver plays a key role in the inflammatory response during major surgery or infection. The influence of age on liver function and hepatic acute phase protein (APP) synthesis should be serially studied in elderly patients undergoing major abdominal surgery. Prospective and descriptive study over 3 days. Clinical investigation in the operating room and surgical intensive care unit (ICU) of a tertiary care hospital. 42 consecutive patients were grouped according to age: less than 60 years ("adult") or over 65 years ("elderly") and prospectively studied. All patients received standardized general anesthesia and were treated afterwards according to the standard protocols of our ICU. Intensivists caring for the patients were not involved in the study and were blinded to data analysis. Concentrations of interleukin (IL)-6, serum amyloid A (SAA), C-reactive protein (CRP), alpha1-antitrypsin (alpha1-AT), and haptoglobin were measured to assess the APP response. Liver function was evaluated by the monoethylglycinexylidide (MEGX) test and by measuring alpha-glutathione S-transferase (alpha-GST). All measurements were performed at induction of anesthesia (T0), at the end of surgery (T1), and 2 h (T2), 24 h (T3), and 48 h (T4) postoperatively. There was no difference in the incidence of postoperative septic complications between the two groups. Baseline values of IL-6 and the four APPs were normal in all patients and did not differ between the groups. IL-6 levels increased significantly in all patients at T1 and T2, with a significantly higher increase in the older patients (elderly: from 7.4+/-3.4 pg/ml to 220.6+/-49.5 pg/ml; adult: from 6.2+/-2.5 pg/ml to 189.9+/-36.8 pg/ml). A return to baseline values was seen at T3 in both groups. Concentrations of all APPs, except for haptoglobin, started to increase at T3. Peak concentrations were significantly lower in the elderly patients (elderly: SAA 358+/-133 microg/l, CRP 5.1+/-2.3 mg/dl, alpha1-AT 160+/-96 mg/dl; adult: SAA 444+/-100 microg/l, CRP 8.5+/-3.2 mg/dl, alpha1-AT 223+/-85 mg/dl). Baseline alpha-GST and MEGX concentrations were normal in all patients. Alpha-GST concentrations increased in both groups at T1 and T2, with a significantly higher increase in the older patients (elderly: 3.7+/-1.4 microg/l to 10.2+/-2.9 microg/l; adult 4.5+/-2.1 microg/l to 8.5+/-1.7 microg/l). A return to baseline values was seen at T3 in both groups. MEGX concentrations were significantly lower and abnormal (<50 ng/ml) in the older patients at T3 and T4. Our observations suggest that the postoperative hepatic acute phase response is reduced in elderly patients undergoing major abdominal surgery. The decreased release of liver-synthesized APPs was associated with an impaired hepatocyte function and a disturbance of hepatocellular integrity. Further work needs to be done to determine whether these findings might have an impact on the incidence of postoperative septic complications or prognostic significance for survival in aged patients.

Protein binding of piritramide: influence of various protein concentrations and the postoperative acute phase response.

Piritramide is a lipophilic opioid, which is widely used for postoperative analgesia and analgosedation in Europe. In this study we investigated the influence of various protein concentrations (total protein, alpha1-acid glycoprotein, albumin) and the postoperative acute phase response on the protein binding of piritramide. The influence of various protein concentrations on the protein binding of piritramide was investigated by either diluting the serum samples of five volunteers with isotonic saline or by adding different amounts of alpha1-acid glycoprotein. Albumin binding was measured in a 5% human albumin solution. The impact of the postoperative acute phase response was investigated by obtaining daily serum samples from 18 surgical patients until the third postoperative day, and measuring piritramide protein binding, alpha1-acid glycoprotein, total protein and albumin. There was a significant relationship between piritramide protein binding and the concentrations of total protein and alpha1-acid glycoprotein. The binding to albumin was 88%. During the postoperative acute phase response, the protein binding of piritramide did not change. Serum concentrations of alpha1-acid glycoprotein increased, whereas total protein and albumin decreased. Although there were significant changes in the piritramide-binding proteins, alpha1-acid glycoprotein and albumin, during the postoperative acute phase response, the protein binding of piritramide did not change. Therefore, a change in protein binding, which might be one factor to be considered in determining piritramide dosage in the postoperative period, does not have to be taken into account.

Acute phase and opsonin response in cardiac surgery patients: influence of underlying cardiac disease.

Cardiopulmonary bypass (CPB) leads to an activation of plasma cascade systems, complement activation, and an acute phase response. To evaluate the influence of the underlying cardiac disease on the activation pattern of these systems, we compared inflammatory changes in coronary artery bypass grafting (CABG) patients with patients undergoing aortic valve replacement. We investigated changes of the acute phase proteins alpha 1-proteinase inhibitor and fibrinogen, the unspecific opsonin fibronectin, and the complement components C3c and C4 induced by extracorporeal circulation in 12 patients undergoing aortic valve replacement and in 12 patients undergoing CABG. Concentrations of C3c and C4 decreased in both groups after the onset of CPB and C4 concentration remained below post-induction levels up to 24 h after onset of CPB (p = 0.04). Fibronectin levels dropped immediately before the onset of CPB (p = 0.01), reaching the lowest values after 20 min of extracorporeal circulation. Fibrinogen and alpha 1-proteinase inhibitor levels after induction of anaesthesia were significantly higher in the CABG group and remained higher throughout the entire study period (p < 0.001). As an indicator of a postoperative acute phase response, concentrations of both proteins rose in the postoperative period above post-induction levels (p < 0.02).

Endotoxin-induced cytokine release from whole blood - similarities between monocyte dysfunction in septic disease and during postoperative acute phase response

Plasma levels of endotoxin, TNFα, interleukin-1β (IL-1β), and interleukin-6 (IL-6) as well as the endotoxin-induced release of these cytokines from whole blood were determined in 20 patients after elective aseptic surgery and eight patients suffering from septic disease. Blood samples were drawn before surgery as well as once daily over 7 days postoperatively. Endotoxin plasma levels increased on the day of the operation from 0.025 ± 0.005 EU/ml to 0.099 ± 0.022 EU/ml and remained elevated for 1 day. No changes were noted in the plasma levels of TNFα and IL-1. Levels of IL-6 increased to 198 ± 52 pg/ml on the day of the operation, while the release of TNFα and IL-6 markedly declined after whole blood was stimulated with endotoxin. The difference between basal and stimulated TNF values amounted to 505 ± 129 pg/ml preoperatively and 132 ± 41 pg/ml after the operation and 297 ± 28 pg/ml and 137 ± 43 pg/ml for IL-6. From the second day of the postoperative period onwards, the endotoxin-induced release of IL-6 was higher than the preoperative values. The results of whole blood stimulation in patients with sepsis were similar to those achieved directly after elective surgery. The cytokine release of TNFα, IL-1β, and IL-6 was reduced. We conclude that, during the early aseptic acute phase reaction, the changes in the functioning of monocytes resemble - qualitatively - those occurring during septic disease, and that this may be related to endotoxemia originating in the gastrointestinal tract.

The post operative acute phase response is uninfluenced by nutritional status : [formula omitted], G A Young, M J McMahon, University Department of Surgery, The General Infirmary, Leeds, UK

The post operative acute phase response is uninfluenced by nutritional status : [formula omitted], G A Young, M J McMahon, University Department of Surgery, The General Infirmary, Leeds, UK