Enhanced recovery pathways in colorectal surgery: a consensus paper by the Associazione Chirurghi Ospedalieri Italiani (ACOI) and the PeriOperative Italian Society (POIS).

Enhanced Recovery After Surgery (ERAS) pathway is a multi-disciplinary, patient-centered protocol relying on the implementation of the best evidence-based perioperative practice. In the field of colorectal surgery, the application of ERAS programs is associated with up to 50% reduction of morbidity rates and up to 2.5 days reduction of postoperative hospital stay. However, widespread adoption of ERAS pathways is still yet to come, mainly because of the lack of proper information and communication. Purpose of this paper is to support the diffusion of ERAS pathways through a critical review of the existing evidence by members of the two national societies dealing with ERAS pathways in Italy, the PeriOperative Italian Society (POIS) and the Associazione Italiana Chirurghi Ospedalieri (ACOI), showing the results of a consensus development conference held at Matera, Italy, during the national ACOI Congress on June 10, 2019.

Supplementation with non-fibrous carbohydrates reduced fiber digestibility and did not improve microbial protein synthesis in sheep fed fresh forage of two nutritive values.

To determine whether non-fibrous carbohydrate (NFC) supplementation improves fiber digestibility and microbial protein synthesis, 18 Corriedale ewes with a fixed intake level (40 g dry matter (DM)/kg BW0.75) were assigned to three (n = 6) diets: F = 100% fresh temperate forage, FG = 70% forage + 30% barley grain and FGM = 70% forage + 15% barley grain + 15% molasses-based product (MBP, Kalori 3000). Two experimental periods were carried out, with late (P1) and early (P2) vegetative stage forage. For P2, ewes were fitted with ruminal catheters. Forage was distributed at 0900 h, 1300 h, 1800 h and 2300 h, and supplement added at 0900 h and 1800 h meals. Digestibility of the different components of the diets, retained N and rumen microbial protein synthesis were determined. At the end of P2, ruminal pH and N-NH3 concentration were determined hourly for 24 h. Supplementation increased digestibility of DM (P < 0.001) and organic matter (OM; P < 0.001) and reduced NDF digestibility (P = 0.043) in both periods, with greater values in P2 (P = 0.008) for the three diets. Daily mean ruminal pH differed (P < 0.05) among treatments: 6.33 (F), 6.15 (FG) and 6.51 (FGM). The high pH in FGM was attributed to Ca(OH)2 in MBP. Therefore, the decreased fiber digestibility in supplemented diets could not be attributed to pH changes. The mean ruminal concentration of N-NH3 was 18.0 mg/dl, without differences among treatments or sampling hours. Microbial protein synthesis was greater in P2 (8.0 g/day) than in P1 (6.1 g/day; P = 0.006), but treatments did not enhance this parameter. The efficiency of protein synthesis tended to be lower in supplemented groups (16.4, 13.9 and 13.4 in P1, and 20.8, 16.7 and 16.2 g N/kg digestible OM ingested in P2, for F, FG and FGM, respectively; P = 0.07) without differences between supplements. The same tendency was observed for retained N: 2.55, 1.38 and 1.98 in P1, and 2.28, 1.23 and 1.10 g/day in P2, for F, FG and FGM, respectively; P = 0.05). The efficiency of microbial protein synthesis was greater in P2 (P = 0.007). In conclusion, addition of feeds containing NFCs to fresh temperate forage reduced the digestibility of cell walls and did not improve microbial protein synthesis or its efficiency. An increase in these parameters was associated to the early phenological stage of the forage.

The effect of intravenous insulin infusion on renal blood flow in conscious sheep is partially mediated by nitric oxide but not by prostaglandins.

To test the effect of insulin on renal perfusion and the participation of NO and PG as mediators of this response, renal blood flow (RBF) was measured in sheep (n = 8) implanted with ultrasonic flow probes around renal arteries and with a systemic arterial pressure (SAP, n = 4) telemetry device. Three protocols were performed: 1) RBF and SAP were recorded (0800 to 1800 h) in fed and fasted sheep, with the latter receiving intravenous (i.v.) infusions (0.5 mL/min) of insulin at 2 or 6 mU/(kg·min); 2) fasted sheep received i.v. infusions of either an inhibitor of NO synthesis (N(G)-nitro-L-arginine methyl ester, L-NAME) alone [0.22 mg/(kg·min), 1000 to 1200 h] or L-NAME (1000 to 1200 h) + insulin during the second hour (6 mU/(kg·min), 1100 to 1200 h); and 3) the same protocol was followed as in protocol 2, substituting L-NAME with ketoprofen [0.2 mg/(kg·min)], a cyclooxygenase inhibitor. In all protocols, plasma insulin and glucose were determined. During insulin administration, euglycemia was maintained and hypokalemia was prevented by infusing glucose and KCl solutions. After the onset of meals, a long-lasting 18% increase in RBF and a 48% insulin increase were observed (P < 0.05), without changes in SAP. Low- and high-dose insulin infusions increased RBF by 19 and 40%, respectively (P < 0.05). As after meals, the increases in RBF lasted longer than the insulin increase (P < 0.05). The L-NAME infusion decreased RBF by 15% (P < 0.05); when insulin was added, RBF increased to preinfusion values. Ketoprofen decreased RBF by 9% (P < 0.05); when insulin was added, RBF increased to 13% above preinfusion values (P < 0.05). In no case was a modification in SAP or glucose noted during the RBF changes. In conclusion, insulin infusion mimics the meal-dependent increase in RBF, independent of SAP, and lasts longer than the blood insulin plateau. The RBF increase induced by insulin was only partially prevented by L-NAME. Ketoprofen failed to prevent the insulin-dependent RBF increase. Both facts suggested that complementary vasodilatatory agents accounted for the insulin effect on sheep renal hemodynamics.

Roles of eating, rumination, and arterial pressure in determination of the circadian rhythm of renal blood flow in sheep.

To assess the roles of feeding behavior (eating and rumination) and systemic arterial pressure (SAP) on determination of the circadian rhythm of renal blood flow (RBF), 20 sheep fitted with ultrasonic flow-metering probes around both renal arteries and a submandibular balloon to monitor jaw movements (6 of them with a telemetry measurement system into the carotid artery for SAP recording), were successively assigned to 6 feeding patterns: once daily in the morning (0900 to 1100 h), afternoon (1700 to 1900 h), or evening (1900 to 2100 h); twice daily at 0900 to 1100 h and 1700 to 1900 h; ad libitum (food renewed each 2 h); and fasting (40 h). All protocols were carried out in autumn-winter, and the fasting pattern was repeated in spring-summer to evaluate the effect of the daylight length on RBF. In the once-daily feeding patterns, a rapid increase in RBF (P < 0.05 vs. 1-h prefeeding mean values) subsequent to the onset of meals was observed, followed by a progressive increase (P < 0.05), reaching a maximum 4 to 6 h after the beginning of eating, and a subsequent gradual decline until the next meal [differences vs. prefeeding values were no longer significant after 11 h (morning pattern), 13 h (afternoon pattern), and 15 h (evening pattern) from the beginning of eating]. In the twice-daily feeding pattern, each meal was also followed by an increase in RBF (P < 0.05 vs. prefeeding values), reaching a maximum 3 to 5 h after the onset of meals, and a posterior decline [differences vs. prefeeding values were no longer significant after 8 h (morning meal) and 5 h (afternoon meal) from the beginning of eating]. In the ad libitum feeding, no apparent rhythm in RBF was found. During fasting, a progressive reduction of RBF was observed from 2 h after the beginning of fasting (P < 0.05 vs. the mean value of the first fasting hour), with a slight rebound (P < 0.05) lasting several hours from approximately 0700 h in autumn-winter and approximately 0500 h in spring-summer. No change in the RBF profile was observed in association with rumination. Except during meals, no correlation was found between RBF and SAP. A detailed description of RBF and SAP recordings is presented. In conclusion, results showed a circadian rhythm of RBF determined by eating behavior, but not by rumination, that was independent of blood pressure and that seemed superimposed on a primary lighting-cycle-dependent RBF rhythm.

Determination of parotid sulfate secretion in sheep by means of ultrasonic flow probes.

The bilateral output of sulfate in parotid saliva, the relationship with its plasma level and with parotid flow, and its variation according to feeding behavior were determined in ad libitum, normal-sulfate (0.28% DM)-fed sheep (n = 6) using a transit time ultrasonic flow meter system to measure salivary flow. Ultrasonic flow meter probes were bilaterally implanted, under general anesthesia, around parotid ducts previously fitted through their oral ends with nonobstructive sampling catheters. Salivary flows were continuously recorded during 24 h, and saliva and blood samples for sulfate determinations were obtained hourly. Jaw movements were monitored with the submandibular balloon technique. The sulfate concentration in parotid saliva (mean of the group = 4.9 +/- 3.7 microg/mL) showed high variability between sheep (individual means from 0.4 +/- 0.3 to 9.3 +/- 5.9 microg/mL) and averaged 12.3% of the more stable plasma level (41.2 +/- 8.1 microg/mL). Pronounced intraindividual variations were also evident (0.1 to 26.3 microg of sulphate/mL of parotid saliva), in strong association with the fluctuations of salivary output. In 4 sheep, a decreasing exponential relationship was observed between parotid sulfate concentration and salivary secretion rate (r2 = 0.36, P < 0.01). This fact and the absence of a relationship between sulfate levels in plasma and in saliva suggest a sulfate secretory process during the passage of primary saliva through the ductal tree of the gland. The greatest rates of bilateral salivary sulfate output were observed during feeding (14.1 +/- 14.0 microg/min) and rumination (12.7 +/- 11.0 microg/min). Nevertheless, 49% of the sulfate output in parotid saliva was present during rest, as a result of the length of the resting times. The contribution of parotid sulfate to the ruminal S pool was highly variable and averaged 13.2 mg/d, representing less than 1% of the S intake. In conclusion, the accurate, reliable, nonobstructive, and bilateral salivary flow monitoring, using a previously characterized ultrasonic flow meter technique, allowed a detailed determination of the secretory dynamics of sulfate in parotid saliva, without disturbing the animal's routine or altering the physiological regulation of salivary output. The results indicated that, in the absence of S deficiency, the recycling of sulfate via saliva seems not to be a major factor in sheep nutrition.

Determination of parotid urea secretion in sheep by means of ultrasonic flow probes and a multifactorial regression analysis.

For determination of the dynamics of parotid urea secretion in conscious sheep, a previously standardized transit time ultrasonic flow metering system was used to measure bilateral parotid flow. Six ewes fed for ad libitum consumption were prepared under halothane anesthesia with ultrasonic probes around both parotid ducts; these ducts were also cannulated orally. After probe encapsulation (8 d), parotid flows were recorded during 24 h, and samples of saliva and blood for urea determination were obtained hourly. Jaw movements were recorded by means of a submandibular balloon to monitor feeding behavior. Urea concentration in parotid saliva was 60 to 74% of that in plasma (a positive linear correlation existed) and was poorly influenced by the parotid flow. The amount of urea secreted with parotid saliva was directly related to the salivation rate. To calculate the urea secretion in parotid saliva, a multiple linear regression model was developed from computer-calculated parotid flows over 1-min periods and plasma urea concentration. The model was accurate because the plot of calculated vs measured values was not significantly different from the line of identity. The daily parotid urea N varied from .35 to 1.02 g among ewes. The higher urea secretion rate found during rumination and eating (1.32+/-.42 and .98 +/-.33 mg/min, respectively) vs. during rest (.60+/-.39 mg/ min, P<.05) was due to higher salivation rates (5.17 +/-1.46, 3.56+/-.90, and 2.04+/-.52 mL/min, respectively, P<.05) rather than to changes in saliva urea concentrations (saliva:plasma urea ratio = .65+/-.04, .67+/-.04, and .68+/-.03, respectively). Of the daily parotid urea output, 40.8% was secreted during rest. The contribution of parotid urea N to the ruminal N pool was relatively small (1.2 to 3.7% of the N intake, which was 23.0 to 33.6 g/d). These techniques allowed direct and precise measurements of parotid urea secretion without disturbing the animal or altering the physiological regulation of salivary secretion.

Micropuncture study on urea movements in the kidney cortical tubules of low protein fed sheep.

Micropuncture studies of late proximal, early and late distal cortical tubules were carried out on kidneys of normal (NP) and low (LP) protein fed sheep in order to investigate the participation of these segments in the urea sparing induced by protein restriction in the diet. A low protein diet induced significant reductions in the fractional (-54%) and total (-84%) urea excretion, revealing an enhanced capacity for urea conservation. Micropuncture data did not show any difference in the proximal tubule functions between both groups of sheep. In distal cortical tubules the fractional delivery of urea (early distal, 0.61 +/- 0.06 for NP and 0.77 +/- 0.06 for LP sheep, not significant (NS); late distal, 0.45 +/- 0.07 for NP and 0.71 +/- 0.09 for LP sheep, P < 0.05) showed a relatively larger amount of urea present in the late distal tubule of protein restricted sheep. The tubular fluid-to-plasma inulin ratio in the late distal tubule was found to be lower in LP sheep (4.33 +/- 0.23 versus 8.58 +/- 0.9 in NP sheep, P < 0.01). The tubular flow rate, reduced in the early distal tubules of LP sheep (10.87 +/- 0.99 versus 18.92 +/- 2.58 nL.min-1 in NP sheep, P < 0.05), was not different in the late distal tubules from values in normally fed animals (6.65 +/- 0.90 versus 7.73 +/- 0.94 nL.min-1 in NP sheep, NS). These findings suggest a decreased distal water reabsorption coincident with the relatively larger amounts of intraluminal urea in LP sheep. This relatively larger urea delivery to the initial collecting duct could increase the subsequent urea reabsorption in protein restricted sheep.

Parotid secretion daily patterns and measurement with ultrasonic flow probes in conscious sheep.

Five sheep under halothane anesthesia were prepared with bilateral transit time ultrasonic flow probes around the parotid ducts. The ducts were fitted with non-obstructive sampling catheters through their oral ends. After probe encapsulation (8 days), salivary flows were continuously recorded (4-5 days, dual-channel ultrasonic flowmeter). For rumination, eating, resting and drinking periods, respectively, the parotid daily outputs recorded were 1.96 +/- 0.57, 0.97 +/- 0.34, 2.84 +/- 0.41 and < 0.041 and bilateral flow rates were 6.76 +/- 0.70, 5.63 +/- 1.42, 2.50 +/- 0.58 and 1.69 +/- 0.88 ml min-1. An ipsilateral secretory reflex was evident when the sheep changed chewing side during rumination (4.44 +/- 0.96 ml min-1 ipsilateral vs 2.63 +/- 0.90 ml min-1 contralateral flow, P < 0.01). Secretory patterns are described in detail during rest, eating, drinking and rumination periods. The pH of parotid saliva (8.36 +/- 0.14) and the osmolality (273.8 +/- 9.9 mosmol kg-1) were independent of secretory rates. In situ probe calibration showed high accuracy (0-9%). The main advantages of the technique are its accuracy and good tolerance, duct integrity and maintenance of nervous supply, minimal surgery, uninterrupted salivary flow, simultaneous bilateral measurements and precise flow monitoring, permitting detailed observations.

Renal response of sheep fed a low protein diet to intraportal infusion of arginine and glycine.

The renal effects of infusions of arginine and glycine into the portal vein were studied in the anaesthetized sheep with a reduced glomerular filtration rate (GFR) after 6 weeks of low dietary protein intake. Arginine significantly elevated urine flow (V), whole kidney GFR and the amount of urea excreted (UureaV) concomitantly with plasma urea level (P(urea)) without changes in fractional urea excretion (FEurea). Sheep infused with glycine showed significantly increased urinary flow only. Free-flow micropuncture of the late proximal tubule revealed that both the fluid flow and single nephron GFR were increased by arginine without any significant changes in tubular fluid to plasma inulin ratio. There was no effect of glycine on the micropuncture parameters of the sheep kidney. These results suggest that the synthesis of urea from arginine in the liver and its subsequent delivery to the kidney may be involved in the regulation of dietary induced changes of the glomerular filtration rate in sheep.

[Existence of an antidiuretic reflex in the sheep during food intake]. / Existence d'un réflexe antidiurétique pendant la prise alimentaire chez le mouton.

The effect of eating on glomerular filtration and urine flow was studied in the sheep. Glomerular filtration rate was reduced during eating but the effect disappeared when food was removed. Urine flow showed the same evolution but, after ingestion was stopped, it returned later than glomerular filtration to control values. During the early phases of feed ingestion, an anticipatory anti-diuretic reflex therefore exists. The anti-diuretic response is probably dependent on a simultaneous decrease in glomerular filtration. But the temporary delay between the recovery of glomerular filtration and urine flow after feed is removed suggests the existence of a second factor responsible for the lowered urine flow.

Urea recycling from the renal pelvis in sheep: a study with [14C]urea.

To test the hypothesis that urea can be recycled from the renal pelvis, [14C]urea diluted in native urine (1 microCi/ml) was perfused (0.5 ml/min) into one of the pelvises of sheep fed either normal (NP) or low (LP)-protein diets. Blood samples were obtained from the ipsilateral renal vein and from the carotid artery throughout the perfusions. 14C activity determinations in urine and plasma demonstrated a flux of [14C]urea from the pelvis to renal vein blood (40,000 in NP and 130,000 disintegrations/min in LP sheep, P less than 0.01). The corresponding flux of native urea was only 1.5 times higher in NP than in LP sheep (6.8 +/- 1.1 vs. 4.7 +/- 2.9 mumol/min, not significant) despite their 8 times higher urinary concentration of urea. The fraction of filtered urea that was reabsorbed in the pelvis was larger in LP sheep (7.5 +/- 3.7 vs. 1.9 +/- 0.7% in NP sheep, P less than 0.05). A fraction of urea is thus actually recycled from the renal pelvis in sheep, and this pelvic retention is enhanced in LP animals. The importance of this phenomenon in the nitrogen economy is discussed.

[Renal extraction of para-aminohippurate and inulin from sheep on low-protein diets]. / Extraction rénale du para-aminohippurate et de l'inuline chez le mouton carencé en protéines.

In sheep fed low-protein diets, renal PAH and inulin extractions are not affected by the fall in plasma urea level or in the renal plasma flow itself. The noted reduction in glomerular filtration rate is not due to a preglomerular shunt of arterial blood since the filtration fraction does not vary by comparison to sheep on regular diets. Thus, the reduction in renal plasma flow (PAH clearance), induced by low protein rations, is not dependent on any change in PAH extraction. This reduction is probably responsible for the simultaneous decrease of glomerular filtration.

[Renal plasma flow and glomerular filtration in conscious sheep: effect of a free-protein diet]. / Débit plasmatique rénal et filtration glomérulaire chez le mouton vigile: influence d'un régime carencé en protéines.

In conscious sheep fed a low protein diet, the urinary flow rate and glomerular filtration rate were reduced. This reduction was not linked to a low blood urea level.

[Diuresis, renal plasma flow and glomerular filtration in conscious and anesthetized sheep: the effects of a diet deficient in proteins]. / Diurèse, débit plasmatique rénal et filtration glomérulaire chez le mouton vigile et anesthésié: effets d'un régime carencé en protéines.

Determinations of renal plasma flow (RPF), glomerular filtration rate (GFR) and urine flow in sheep fed low protein diets have yielded controversial data. In the present experiment, 8 sheep were fed a regular diet and another 6 received a low protein ration. Water intake and urine output were measured over 10 days. RPF and GFR were determined on 2 consecutive days. The latter determinations were repeated on 5 anaesthetized animals (sodium thiopental) in each group. An important increase in water intake (58%) and urine output (98%) was observed in the sheep on the low protein diet. In these animals, blood urea averaged 0.1 g/l. Urine output was greater (with a lower osmolarity) when the blood urea level was the lowest. RPF and GFR were significantly lower in the sheep on the low protein diet (RPF: 13.5 versus 28.1 ml/min/kg in the control animals; GFR: 1.61 versus 4.01 ml/min/kg); no relationship could be established with the blood urea level. The only effect of the anaesthesia was a reduction in RPF, of the same magnitude in both groups of sheep (about 35%). In conclusion, when sheep are fed a low protein diet, the volume of plasma processed through the kidney is decreased. In the present experiment, the increased urine flow and the lowered urinary osmolarity indicate an impaired renal concentrating ability. Barbiturate anaesthesia does not affect this phenomenon.

[Augmentation of the urea retention capacity of the kidney in protein-deficient sheep: role of the kidney pelvis]. / Augmentation du pouvoir de rétention rénale de l'urée chez le mouton carencé en protéines: rôle du bassinet.

Sheep fed a low-protein diet reduced renal urea excretion. An important fraction of urea perfused into the renal pelvis via the ureter, is reabsorbed through the pelvic epithelium.

[Kidney retention of urea in sheep on a hypoprotein diet: study by retrograde perfusion of urea in the kidney pelvis]. / L'épargne rénale d'urée chez le mouton en régime hypoprotéique: étude par perfusion rétrograde d'urée dans le bassinet.

In order to study the role of the renal pelvis on urea sparing in sheep fed low protein diets, the pelvis was perfused through the ureter with 1M and 3M urea solutions. Eight ewes were used: four on a regular diet (total nitrogen 188.7 g.kg-1 dry matter) and the other four on a low protein diet (total nitrogen 109.4 g.kg-1 dry matter). On each animal, perfusions were performed on one kidney; the other one was kept as a control. Fractional excretion of urea (TEu) and urea (Cu), inulin, para-aminohippurate and osmolar clearances, were determined during five experimental periods of 30 min each (T = control, 1M = perfusion with 1M urea solution, R1 = first period of recovery, 3M = perfusion with 3M urea solution, R2 = second period of recovery). 1. During control periods sheep on low protein diet have a greater capacity of urea retention than sheep on regular diet, under antidiuretic conditions (inulin U/P = 200). The following data (means +/- S.D.) are all reduced in animals on low protein diet: TEu by 36% (0.38 +/- 0.19 vs. 0.59 +/- 0.28 for normal protein sheep, p less than 0.05), Cu by 55% (0.50 +/- 0.19 vs. 1.15 +/- 0.49 ml.min-1.kg-1 for normal sheep, p less than 0.01) and amount of urea excreted by 80% (2.1 +/- 0.7 vs. 10.4 +/- 2.7 mg.min-1 for normal sheep, p less than 0.01). 2. The linear regression analysis of the relationship between tubular reabsorption of urea and its filtered amount shows that the capacity of urea retention is significantly higher in low protein sheep and that the difference between the two groups is greater as the filtered amount increases. Following 1M and 3M perfusions, the capacity of urea reabsorption by the perfused kidneys is significantly decreased in low protein animals whereas there is no change in the normal ones. The result is that perfused kidneys of the low protein sheep increase the amount of urea excreted during these periods: urine concentration of urea (Uu) increases by 55% during R1 and by 144% during R2, TEu increases by 60% during R1 and by 147% during R2 and Cu increases by 40% during R1 and by 95% during R2, without any variation of urine flow rate. These changes could be understood, provided that an important transfer of the perfused urea to the renal medulla in the low protein sheep would reduce the concentration gradients which enhance urea passive reabsorption from the collecting ducts.(ABSTRACT TRUNCATED AT 250 WORDS)