Forecasting transitions in the state of food security with machine learning using transferable features.

Food insecurity is a growing concern due to man-made conflicts, climate change, and economic downturns. Forecasting the state of food insecurity is essential to be able to trigger early actions, for example, by humanitarian actors. To measure the actual state of food insecurity, expert and consensus-based approaches and surveys are currently used. Both require substantial manpower, time, and budget. This paper introduces an extreme gradient-boosting machine learning model to forecast monthly transitions in the state of food security in Ethiopia, at a spatial granularity of livelihood zones, and for lead times of one to 12 months, using open-source data. The transition in the state of food security, hereafter referred to as predictand, is represented by the Integrated Food Security Phase Classification Data. From 19 categories of datasets, 130 variables were derived and used as predictors of the transition in the state of food security. The predictors represent changes in climate and land, market, conflict, infrastructure, demographics and livelihood zone characteristics. The most relevant predictors are found to be food security history and surface soil moisture. Overall, the model performs best for forecasting Deteriorations and Improvements in the state of food security compared to the baselines. The proposed method performs (F1 macro score) at least twice as well as the best baseline (a dummy classifier) for a Deterioration. The model performs better when forecasting long-term (7 months; F1 macro average = 0.61) compared to short-term (3 months; F1 macro average = 0.51). Combining machine learning, Integrated Phase Classification (IPC) ratings from monitoring systems, and open data can add value to existing consensus-based forecasting approaches as this combination provides longer lead times and more regular updates. Our approach can also be transferred to other countries as most of the data on the predictors are openly available from global data repositories.

Transversus abdominis plane block or intravenous lignocaine in open prostate surgery: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Transversus abdominis plane block (TAP) and intravenous lignocaine are two analgesic techniques frequently used after abdominal surgery. We hypothesized that these two techniques improve post-operative analgesia after open prostate surgery and sought to compare their efficacy on immediate post-operative outcome after open prostate surgery. METHODS: After ethics committee approval, 101 patients were enrolled in this prospective study and randomly allocated to receive bilateral ultrasound-guided TAP (n = 34), intravenous lignocaine (n = 33) or placebo (n = 34). In addition, intravenous paracetamol was given every 6 h. The primary endpoint was the cumulative opioid consumption during the first 48 post-operative hours (median[IQR]). Secondary endpoints included pain scores at rest and upon coughing, need for rescue tramadol, incidence of post-operative nausea and vomiting (PONV), recovery of bowel function and incidence of bladder catheter-related discomfort. RESULTS: Cumulative piritramide consumption after 48 h was 28 [23] mg in the control group, 21 [29] mg in the TAP group and 21 [31] mg in the lignocaine group (P = 0.065). There was no significant difference in post-operative pain scores between groups. The proportions of patients requiring rescue tramadol, experiencing PONV or bladder catheter-related discomfort were similar in each group. Recovery of bowel function was also similar in the three groups. CONCLUSIONS: Our study suggests that TAP block and intravenous lignocaine do not improve the post-operative analgesia provided by systematic administration of paracetamol after open prostatectomy.

Recruitment of lung volume during surgery neither affects the postoperative spirometry nor the risk of hypoxaemia after laparoscopic gastric bypass in morbidly obese patients: a randomized controlled study.

BACKGROUND: Intraoperative recruitment manoeuvres (RMs) combined with PEEP reverse the decrease in functional residual capacity (FRC) associated with anaesthesia and improve intraoperative oxygenation. Whether these benefits persist after operation remains unknown. We tested the hypothesis that intraoperative RMs associated with PEEP improve postoperative spirometry including FRC and reduce the incidence of postoperative hypoxaemia in morbidly obese (MO) patients undergoing laparoscopic gastric bypass. METHODS: After IRB approval and informed consent, 50 MO patients undergoing laparoscopic gastric bypass under volume-controlled ventilation (tidal volume 6 ml kg(-1) of IBW) were randomly ventilated with either 10 cm H2O PEEP or with 10 cm H2O PEEP and one RM carried out after induction of pneumoperitoneum, and another after exsufflation. Anaesthesia and analgesia were standardized. Spirometry was assessed before operation and 24 h after surgery. Postoperative oxygenation and the apnoea-hypopnoea index (AHI) were recorded during the first postoperative night. RESULTS: Age, BMI, and STOP BANG score were similar in both groups. FRC decrease after surgery was minimal [0.15 (0.14) litre in control and 0.38 (0.19) litre in the RM group] and similar between the groups (P=0.35). FVC, FEV1, mean [Formula: see text], percentage of time spent with [Formula: see text] below 90%, and AHI did not differ significantly between the groups. CONCLUSIONS: This study demonstrates that when added to a protective mechanical ventilation combining low tidal volume and high PEEP, two RMs do not improve postoperative lung function including FRC, arterial oxygenation, and the incidence of obstructive apnoea in MO patients after laparoscopic upper abdominal surgery. CLINICAL TRIAL REGISTRATION: EudraCT 2011-000999-33.

Intravenous lidocaine infusion reduces bispectral index-guided requirements of propofol only during surgical stimulation.

BACKGROUND: I.V. lidocaine reduces volatile anaesthetics requirements during surgery. We hypothesized that lidocaine would also reduce propofol requirements during i.v. anaesthesia. METHODS: A randomized controlled study of 40 patients tested the effect of i.v. lidocaine (1.5 mg kg(-1) then 2 mg kg(-1) h(-1)) on propofol requirements. Anaesthesia was maintained with remifentanil and propofol target-controlled infusions (TCI) to keep the bispectral index (BIS) around 50. Effect-site concentrations of propofol and remifentanil and BIS values were recorded before and after skin incision. Data were analysed using anova and mixed effects analysis with NONMEM. Two dose-response studies were then performed with and without surgical stimulation. Propofol TCI titrated to obtain a BIS around 50 was kept constant. Then patients were randomized into four groups: A, saline; B, 0.75 mg kg(-1) bolus then infusion 1 mg kg(-1) h(-1); C, 1.5 mg kg(-1) bolus and infusion 2 mg kg(-1) h(-1); and D, 3 mg kg(-1) bolus and infusion 4 mg kg(-1) h(-1). Lidocaine administration coincided with skin incision. BIS values and haemodynamic variables were recorded. Data were analysed using linear regression and two-way anova. RESULTS: Lidocaine decreased propofol requirements (P<0.05) only during surgery. In the absence of surgical stimulation, lidocaine did not affect BIS nor haemodynamic variables, whereas it reduced BIS increase (P=0.036) and haemodynamic response (P=0.006) secondary to surgery. CONCLUSIONS: The sparing effect of lidocaine on anaesthetic requirements seems to be mediated by an anti-nociceptive action.

Norepinephrine and ephedrine do not counteract the increase in cutaneous microcirculation induced by spinal anaesthesia.

BACKGROUND: Neuraxial anaesthesia improves tissue perfusion and tissue oxygen tension. Vasodilation induced by this technique may result in hypotension requiring the administration of vasoactive drugs. The use of peripheral vasoconstrictors might counteract the improved tissue perfusion and its potentially beneficial effects. We therefore investigated the effect of i.v. norepinephrine and ephedrine on skin perfusion using laser-Doppler flowmetry (LDF) in patients during spinal anaesthesia. METHODS: Skin blood flow expressed in perfusion units (PU) provided by LDF was measured simultaneously at the foot and the manubrium levels in 44 patients during spinal anaesthesia with a sensory level below T5. Norepinephrine infusion was then titrated to normalize mean arterial pressure (MAP) in 23 patients (Group NOR). Ephedrine (max. 10 mg) was administered in 21 patients (Group EPH). Changes in relative PU were compared between the two sites of measurements in each group during drug administration. The same doses of norepinephrine were assessed in 11 normal volunteers to assure comparable vasoreactivity at the foot and manubrium levels. RESULTS: Spinal anaesthesia resulted in a 10% decrease in MAP (P<0.001), an increase in relative PU values at the foot level (P<0.001), and a decrease at the sternum level (P<0.05). Norepinephrine and ephedrine produced a significant increase in relative PU values at the foot level when compared with the sternum level (NOR: P=0.02; EPH: P=0.0035). In volunteers, norepinephrine decreased cutaneous perfusion similarly at the manubrium and foot levels. CONCLUSIONS: Improved skin perfusion induced by spinal anaesthesia was not counteracted by the use of norepinephrine or ephedrine.

Effect of celecoxib combined with thoracic epidural analgesia on pain after thoracotomy.

BACKGROUND: Thoracotomy results in severe postoperative pain potentially leading to chronic pain. We investigated the potential benefits of oral celecoxib on postoperative analgesia combined with thoracic epidural analgesia (TEA). METHODS: Forty patients undergoing thoracotomy were included in this prospective, randomized, double-blind, placebo-controlled study. General anaesthesia was standardized. Patient-controlled epidural analgesia (T4-T5) was used during 48 h after surgery (ropivacaine 2 mg ml(-1) with sufentanil 0.5 microg ml(-1)). Patients were allocated to receive oral celecoxib or placebo from the evening before surgery until 48 h after operation. Postoperative pain scores, respiratory function, and morbidity were compared between the two groups. RESULTS: Postoperative pain scores at rest (P=0.026) and during coughing (P=0.021) were lower and patient satisfaction was greater (P=0.0033) in the celecoxib group. Consumption of the local anaesthetic solution was comparable between groups. Postoperative restrictive pulmonary syndrome and morbidity were comparable between groups. CONCLUSIONS: Celecoxib improves postoperative analgesia provided by TEA after thoracotomy.

Postoperative respiratory problems in morbidly obese patients.

Morbid obesity results in a restrictive pulmonary syndrome including decreased functional residual capacity. General anaesthesia further decreases functional residual capacity, and consequently alters gas exchanges more profoundly in morbidly obese patients than in nonobese patients. Moreover, these changes persist longer during the postoperative period, rendering obese subjects vulnerable to postoperative respiratory complications. In this review, we present postoperative measures improving respiratory function of these patients. Whether these measures affect outcome remains however unknown. Patients suffering from obstructive sleep apnoea syndrome deserve special considerations that are briefly described. Finally, the algorithm of the postoperative respiratory management of morbid obese patients used in our institution is provided.

Acute rehabilitation program after laparoscopic colectomy using intravenous lidocaine.

BACKGROUND: The concept of postoperative acute rehabilitation was introduced to accelerate postoperative recovery and improve outcome. We investigated whether intravenous lidocaine infusion, which decreases postoperative pain and speeds the return of bowel function, can be used instead of epidural analgesia in an acute rehabilitation protocol for patients undergoing laparoscopic colectomy. METHODS: Twenty eight consecutive patients scheduled for laparoscopic colectomy were prospectively included in this case series study. Segmental colectomy was performed only for benign pathology. Intraoperative opioid use was restricted. After a bolus injection of lidocaine 1.5 mg x kg(-1), an infusion (2 mg x kg(-1) x h(-1), i.v.) was started before pneumoperitoneum. Balanced analgesia was used to reduce postoperative opioid consumption. Patients were allowed to drink 6 h postoperatively. The day after surgery, patients were allowed to eat a normal breakfast. Enforced mobilisation and ambulation were required from the patients. Our goal was to discharge patients within 3 days after surgery. Postoperative pain was measured. Time to first flatus, defecation, and hospital discharge were recorded. RESULTS: Mean postoperative pain at rest and mobilisation remained below 30 mm on a 100 mm visual analogue scale. Time to first flatus, defecation, and hospital discharge were 29 +/- 13 h, 38 +/- 13 h, and 3.0 +/- 1.0 days, respectively. CONCLUSION: Acute rehabilitation after laparoscopic colectomy using i.v. lidocaine gives similar outcomes to those reported using epidural analgesia.

Supplemental oxygen does not reduce postoperative nausea and vomiting after thyroidectomy.

BACKGROUND: Supplemental intra-operative oxygen 80% halves the incidence of nausea and vomiting after open and laparoscopic abdominal surgery, perhaps by ameliorating intestinal ischaemia associated with abdominal surgery. It is unlikely that thyroid surgery compromises intestinal perfusion. We therefore tested the hypothesis that supplemental perioperative oxygen does not reduce the risk of postoperative nausea and vomiting (PONV) after thyroidectomy. METHODS: One hundred and fifty patients undergoing thyroidectomy were given sevoflurane anaesthesia. After induction, patients were randomly assigned to the following treatments: (i). 30% oxygen, (ii). 80% oxygen, or (iii). 30% oxygen with droperidol 0.625 mg. RESULTS: The overall incidence of nausea during the first 24 h after surgery was 48% in the patients given oxygen 30%, 46% in those given oxygen 80%, and 22% in those given droperidol (P=0.004). There were no significant differences between the oxygen 30% and 80% groups in incidence or severity of PONV, the need for rescue antiemetics, or patient satisfaction. Droperidol significantly shortened the time to first meal. CONCLUSIONS: Supplemental oxygen was ineffective in preventing nausea and vomiting after thyroidectomy, but droperidol reduced the incidence.

Hemodynamic changes and catecholamine release during laparoscopic adrenalectomy for pheochromocytoma.

UNLABELLED: We investigated hemodynamics and plasma catecholamine concentrations in eight consecutive patients undergoing laparoscopic adrenalectomy for suspected pheochromocytoma. The same anesthesia protocol was used in all patients: a continuous infusion of sufentanil 0.5 microg x kg(-1) x h(-1) and isoflurane 0.4% (end-tidal) in 50% N2O/O2. Systolic arterial pressure was maintained between 120 and 160 mm Hg by adjusting an infusion of nicardipine, a calcium-channel blocker, while tachycardia (>100 bpm) was treated by 1-mg boluses of atenolol. Hemodynamics (thermodilution technique) and plasma catecholamine concentrations were measured before surgery, after the induction of anesthesia, after turning the patient to the lateral position, during pneumoperitoneum, during tumor manipulation, after adrenalectomy, and at the end of surgery. Two events resulted in significant catecholamine release: creation of the pneumoperitoneum and adrenal gland manipulation. As a consequence, a twofold increase in cardiac output was recorded. Adjustments of nicardipine infusion (2-6 microg x kg(-1) x min(-1)) minimized changes in mean arterial pressure. Beta-adrenergic blockade was necessary in six patients. In conclusion, laparoscopic adrenalectomy for pheochromocytoma results in marked catecholamine release during pneumoperitoneum and tumor manipulation. Titration of a nicardipine infusion allowed easy and quick control of the hemodynamic aberrancies related to these processes. IMPLICATIONS: Pneumoperitoneum during laparoscopy, now used for adrenalectomy, may complicate anesthetic management of patients with pheochromocytoma. In this study, laparoscopic adrenalectomy was associated with catecholamine release during the creation of pneumoperitoneum and tumor manipulation. Adjustments of a nicardipine infusion readily attenuated the subsequent hemodynamic aberrancies.

Hemodynamic changes induced by laparoscopy and their endocrine correlates: effects of clonidine.

OBJECTIVES: We investigated endocrine correlates of the hemodynamic changes induced by carbon dioxide pneumoperitoneum (PNO). We then studied whether clonidine might modulate the hemodynamic changes induced by PNO by reducing release of catecholamines and vasopressin. BACKGROUND: Both mechanical and neurohumoral factors contribute to the hemodynamic changes induced by carbon dioxide PNO. Several mediators have been proposed, but no study has correlated hemodynamic changes with changes in levels of these potential mediators. METHODS: We conducted two studies, each including 20 healthy patients scheduled for elective laparoscopic cholecystectomy. In the first study serial measurements of hemodynamics (thermodilution technique) were done during laparoscopy and after exsufflation. Plasma concentrations of cortisol, catecholamines, vasopressin, renin, endothelin and prostaglandins were measured at the same time points. In the second study patients were randomly allocated to receive 8 microg/kg clonidine infused over 1 h or placebo before PNO. Hemodynamics and plasma levels of cortisol, catecholamines and vasopressin were measured during PNO and after exsufflation. RESULTS: Peritoneal insufflation resulted in a significant reduction of cardiac output (18+/-4%) and increases in mean arterial pressure (39+/-8%) and systemic (70+/-12%) and pulmonary (98+/-18%) vascular resistances. Laparoscopy resulted in progressive and significant increases in plasma concentrations of cortisol, epinephrine, norepinephrine and renin. Vasopressin plasma concentrations markedly increased immediately after the beginning of PNO (before PNO 6+/-4 pg/ml; during PNO 129+/-42 pg/ml; p < 0.05). The profile of vasopressin release paralleled the time course of changes in systemic vascular resistance. Prostaglandins and endothelin did not change significantly. Clonidine significantly reduced mean arterial pressure, heart rate and the increase in systemic vascular resistance. Clonidine also significantly reduced catecholamine concentrations but did not alter vasopressin and cortisol plasma concentrations. CONCLUSIONS: Vasopressin and catecholamines probably mediate the increase in systemic vascular resistance observed during PNO. Clonidine before PNO reduces catecholamine release and attenuates hemodynamic changes during laparoscopy.

Pulmonary function and pain after gastroplasty performed via laparotomy or laparoscopy in morbidly obese patients.

We have compared severely obese patients (body mass index > 35 kg m-2) undergoing laparoscopic or open gastroplasty (n = 15 in each group) to determine if laparoscopy results in any benefit in the obese. Postoperative pain, measured on a 100-mm visual analogue scale, and opioid consumption were recorded during the first two days after operation. Tests of pulmonary function were performed and SpO2 was measured 4 h after surgery and on days 1, 2 and 3 after operation. Pain at rest was similar in the two groups, but in the laparoscopy group, requirements for postoperative opioid were 50% less (P < 0.05). Pain intensity during mobilization and on coughing was significantly less after laparoscopy (differences between mean pain scores in both groups ranged from 20 to 32 mm during mobilization and from 32 to 34 mm during coughing). Forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow rate were reduced significantly less after laparoscopic gastroplasty than after open gastroplasty (on day 1 forced vital capacity was reduced by 50% compared with 64%, forced expiratory volume in 1 s was reduced by 50% compared with 66% and peak expiratory flow rate by 45% compared with 60%). SpO2 values were significantly greater in the laparoscopy group (day 1: mean 95 (SD 2)% vs 91 (5)%; day 3: 97 (1)% vs 94 (3)%). This study suggests that the beneficial effects observed after laparoscopic gastroplasty in morbidly obese patients were similar to those reported after laparoscopic cholecystectomy in non-obese patients.

Effect of bi-level positive airway pressure (BiPAP) nasal ventilation on the postoperative pulmonary restrictive syndrome in obese patients undergoing gastroplasty.

STUDY OBJECTIVE: Upper abdominal surgery results in a postoperative restrictive pulmonary syndrome. Bi-level positive airway pressure (BiPAP System; Respironics Inc; Murrysville, Pa), which combines pressure support ventilation and positive end-expiratory pressure via a nasal mask, could allow alveolar recruitment during inspiration and prevent expiratory alveolar collapse, and therefore limit the postoperative pulmonary restrictive syndrome. This study investigated the effect of BiPAP on postoperative pulmonary function in obese patients after gastroplasty. DESIGN: Prospective controlled randomized study. SETTING: GI surgical ward in a university hospital. PATIENTS: Thirty-three morbidly obese patients scheduled for gastroplasty were studied. INTERVENTION: The patients were assigned to one of three techniques of ventilatory support during the first 24 h postoperatively: O2 via a face mask, BiPAP System 8/4, with inspiratory and expiratory positive airway pressure set at 8 and 4 cm H2O, respectively, or BiPAP System 12/4 set at 12 and 4 cm H2O. Pulmonary function (FVC, FEV1, and peak expiratory flow rate [PEFR]) were measured the day before surgery, 24 h after surgery, and on days 2 and 3. Oxygen saturation by pulse oximeter (SpO2) was also recorded during room air breathing. RESULTS: Three patients were excluded. After surgery, FVC, FEV1, PEFR, and SpO2 significantly decreased in the three groups. On day 1, FVC and FEV1 were significantly improved in the group BiPAP System 12/4, as compared with no BiPAP; SpO2 was also significantly improved. After removal of BiPAP System 12/4, these benefits were maintained, allowing faster recovery of pulmonary function. No significant effects were observed on PEFR. BiPAP System 8/4 had no significant effect on the postoperative pulmonary restrictive syndrome. CONCLUSION: Prophylactic use of BiPAP System 12/4 during the first 24 h postoperatively significantly reduces pulmonary dysfunction after gastroplasty in obese patients and accelerates reestablishment of preoperative pulmonary function.

Pneumothorax during laparoscopic fundoplication: diagnosis and treatment with positive end-expiratory pressure.

Pneumothorax can develop during laparoscopy, particularly during laparoscopic fundoplication, since the left parietal pleura is exposed and can be torn during dissection in the diaphragmatic hiatus. Such an event will result in specific pathophysiologic changes, since CO2, under pressure in the abdominal cavity, will pass into the pleural space. The aim of this study was to document the pathophysiologic changes induced by pneumothorax, and to evaluate the benefit of positive end-expiratory pressure (PEEP) to treat pneumothorax. Forty-six ASA physical status I and II patients scheduled for laparoscopic fundoplication were monitored extensively; heart rate, mean arterial pressure, end-tidal CO2 (PETCO2), oxygen saturation of hemoglobin (Spo2), minute ventilation, tidal volume, dynamic total lung thorax compliance, and airway pressures were recorded. In 25 patients, oxygen uptake, CO2 elimination and arterial blood gases were also measured. Pneumothorax was diagnosed in seven patients. It resulted in the following pathophysiologic changes: decrease in total lung thorax compliance, increase in airway pressures, and increase in CO2 absorption. Consequently, PACO2 and PETCO2 also increased. Spo2, however, remained normal. The use of PEEP largely corrected these respiratory changes. None of these pneumothoraces required drainage. These data suggest that pneumothorax is common during laparoscopic fundoplication. Early diagnosis is possible by simultaneous monitoring of PETCO2, total lung thorax compliance, and airway pressures. Finally, treatment with PEEP provides an alternative to chest tube placement when pneumothorax is secondary to passage of peritoneal CO2 into the interpleural space.

Hemodynamic changes during laparoscopic cholecystectomy.

Hemodynamics during laparoscopic cholecystectomy under general anesthesia (isoflurane in N2O/O2 (50%)) were investigated in 15 nonobese ASA Class I patients by using invasive hemodynamic monitoring including a flow-directed pulmonary artery catheter. During surgery, intraabdominal pressure was maintained automatically at 14 mm Hg by a CO2 insufflator, and minute ventilation was controlled and adjusted to avoid hypercapnia. Hemodynamics were measured before anesthesia, after the induction of anesthesia, after tilting into 10 degrees head-up position, 5 min, 15 min, and 30 min after peritoneal insufflation, and 30 min after exsufflation. Induction of anesthesia decreased significantly mean arterial pressure and cardiac index (CI). Tilting the patient to the head-up position reduced cardiac preload and caused further reduction of CI. Peritoneal insufflation resulted in a significant increase (+/- 35%) of mean arterial pressure, a significant reduction (+/- 20%) of CI, and a significant increase of systemic (+/- 65%) and pulmonary (+/- 90%) vascular resistances. The combined effect of anesthesia, head-up tilt, and peritoneal insufflation produced a 50% decrease in CI. Administration of increasing concentrations of isoflurane, via its vasodilatory activity, may have partially blunted these hemodynamic changes. These results demonstrate that laparoscopy for cholecystectomy in head-up position results in significant hemodynamic changes in healthy patients, particularly at the induction of pneumoperitoneum.

Release from inflamed tissue of a substance with properties similar to corticotropin-releasing factor.

In response to stressors involving tissue injury, pituitary corticotroph secretion of immunoreactive beta-endorphin (iB-END) could be either due to release of hypothalamic factors such as corticotropin-releasing factor (CRF) or to release of a tissue factor from the periphery. In the present experiments, we investigated whether inflamed tissue releases a factor which evokes pituitary secretion of iB-END. In an initial experiment, rats with an inflamed hindpaw due to carrageenan injection had significantly greater levels of circulating iB-END as compared to rats with saline-injected paws. Removal of afferent input, by hindlimb denervation, failed to block the carrageenan-induced increase in iB-END levels. Subcutaneous perfusates were then collected from inflamed and control hindlimbs and applied to rat anterior pituitary cell cultures. Pituitary release of iB-END due to administration of perfusate from inflamed paws was significantly greater than iB-END release due to perfusate from saline-injected paws or to basal release. The releasing activity in the perfusates was blocked in calcium-free medium and was not due to a direct action of carrageenan, bradykinin, substance P or calcitonin gene-related peptide. The results indicate that inflamed tissue releases a CRF-like factor which stimulates iB-END release both in the denervated rat and cultured pituitary cells.

Bradykinin is increased during acute and chronic inflammation: therapeutic implications.

Bradykinin is a potent pain-producing substance, yet little is known about its role in inflammation. The present study measured circulating levels of immunoreactive bradykinin in a clinical model of acute inflammation (oral surgery) and chronic inflammation (rheumatoid arthritis) and in the rat carrageenan model of inflammation. The effects of a kallikrein inhibitor (soybean trypsin inhibitor) on blocking bradykinin synthesis in vitro and its analgesic actions in the rat model were also evaluated. Levels of immunoreactive bradykinin increased threefold to fourfold during oral surgery. Levels were twofold to threefold greater in patients with rheumatoid arthritis compared with control subjects. Levels of immunoreactive bradykinin increased twofold in rats during carrageenan inflammation. Soybean trypsin inhibitor blocked synthesis of bradykinin in vitro and possessed analgesic activity in rats. The results indicate that the bradykinin system is activated during inflammation. Kallikrein inhibitors may represent a new class of analgesic/antiinflammatory drugs.

Opioid analgesia at peripheral sites: a target for opioids released during stress and inflammation?

The peripheral analgesic effects of opiates were evaluated in a rat model of inflammation. The experimental design excluded a potential central nervous system site of action for the observed analgesia. After the injection of carrageenan (CARRA) in the plantar surface of both hind paws, an opiate was injected into one paw and saline was injected into the other paw. The inflamed paws injected with the mu-agonist, fentanyl (0.3 micrograms) or the kappa-agonist, ethylketocyclazocine (10 micrograms) were significantly less hyperalgesic (P less than 0.001 and P less than 0.01, respectively) than were the contralateral inflamed paws injected with saline. At these doses, fentanyl and ethylketocyclazocine were devoid of systemic effects. Another mu-agonist, levorphanol (20, 40, 80, or 160 micrograms) and dextrorphan (160 micrograms), its dextrorotatory isomer, were used next to evaluate opioid specificity. Levorphanol produced a dose-related blockade of CARRA-induced hyperalgesia (P less than 0.005). In contrast, 160 micrograms of dextrorphan was inactive. These results demonstrate that local administration of opiates into an inflamed paw produces a dose-related, stereospecific analgesia restricted to the injected area.