<p>Septic shock is frequently seen in intensive care units and is associated with significant mortality. Endotoxin – a major mediator of the pathophysiologic responses – is released during lysis of Gram-negative bacteria. These responses can be mimicked in the endotoxaemic pig.</p><p>This thesis focuses on the following topics: the inflammatory and pathophysiological responses to various endotoxin doses and infusion patterns; covariations between endotoxin induced inflammatory and pathophysiological responses; whether the biological effects of endotoxin can be modulated by clopidogrel and whether tobramycin or ceftazidime reduce plasma cytokine levels.</p><p>Endotoxin induced linear log-log cytokine and F2-isoprostane responses. Leukocyte and platelet responses, pulmonary compliance, circulatory variables as well as indicators of plasma leakage and hypoperfusion exhibited log-linear responses to the endotoxin dose. Biological responses to endotoxaemia such as inflammation, hypotension, hypoperfusion and organ dysfunction were more expressed when the organism was exposed to endotoxin at a higher rate. These results may facilitate the possibility to choose relevant endotoxin administration, when experiments are set up in order to evaluate certain responses to endotoxaemia.</p><p>Correlation studies between cytokines, leukocytes, platelets and the endotoxin dose were in agreement with the well-known ability of endotoxin to induce cytokine expression and to activate both primary haemostasis and leukocytes. Free radical mediated lipid peroxidation and COX-mediated inflammation correlated to cytokine expression and organ dysfunction in endotoxaemic shock. </p><p>Endotoxaemic pigs pretreated with clopidogrel, exhibited a trend towards less expressed deterioration of renal function, although blocking of ADP-induced primary haemostasis is not a key mediator of endotoxin induced deterioration of renal function.</p><p>Tobramycin did not neutralise the biological effects of endotoxin or the plasma levels of endotoxin, suggesting that these antibiotics do not bind to endotoxin.</p><p>Reduction in IL-6 was greater in pigs treated with ceftazidime and tobramycin as compared with those given saline, indicating a possible anti-inflammatory effect of both antibiotics.</p>

Neuropathic pain of central and peripheral origin presents a substantial clinical problem as it is often resistant to pharmacological treatment. The health related quality of life of 126 patients with peripheral neuropathic pain was studied, to provide a cross sectional description from this point of view. Two generic health-related quality of life instruments; the SF-36 and the Nottingham Health Profile were used together with pain assessments, global rating of health and verbal rating scales of pain and other symptoms, as well as patient descriptors. The analgesic effect of ketamine, lidocaine and morphine were assessed in a double blind, placebo-controlled, randomized study design. Three groups of patients were studied: patients with peripheral neuropathic pain of traumatic origin, patients with central post-stroke pain and patients with neuropathic pain after spinal cord injury. Somatosensory function was examined to see if this could predict response to treatment and to investigate if the drugs caused changes in thermal or mechanical sensibility. The results shows that the intense pain, limited efficacy and tolerability of available treatments, the low overall rating of health, reduced work status and troublesome symptoms constitute a substantial impact on the quality of life for patients with peripheral neuropathic pain. The NMDA-antagonist ketamine yielded substantial pain relief to patients with peripheral neuropathic pain and patients with neuropathic pain after spinal cord injury. However, the reported side effects limit the clinical usefulness of the treatment. Lidocaine did not give significant pain relief to the patients in the three studied groups. Morphine may represent a therapeutic alternative for some patients with central post-stroke pain, although only a small group of this category of patients responded with analgesia. Assessment of baseline somatosensory functions could not be used to identify responders to treatment with either drug, nor did ketamine, lidocaine or morphine cause any changes in thermal or mechanical sensibility.

Septic shock is frequently seen in intensive care units and is associated with significant mortality. Endotoxin – a major mediator of the pathophysiologic responses – is released during lysis of Gram-negative bacteria. These responses can be mimicked in the endotoxaemic pig. This thesis focuses on the following topics: the inflammatory and pathophysiological responses to various endotoxin doses and infusion patterns; covariations between endotoxin induced inflammatory and pathophysiological responses; whether the biological effects of endotoxin can be modulated by clopidogrel and whether tobramycin or ceftazidime reduce plasma cytokine levels. Endotoxin induced linear log-log cytokine and F2-isoprostane responses. Leukocyte and platelet responses, pulmonary compliance, circulatory variables as well as indicators of plasma leakage and hypoperfusion exhibited log-linear responses to the endotoxin dose. Biological responses to endotoxaemia such as inflammation, hypotension, hypoperfusion and organ dysfunction were more expressed when the organism was exposed to endotoxin at a higher rate. These results may facilitate the possibility to choose relevant endotoxin administration, when experiments are set up in order to evaluate certain responses to endotoxaemia. Correlation studies between cytokines, leukocytes, platelets and the endotoxin dose were in agreement with the well-known ability of endotoxin to induce cytokine expression and to activate both primary haemostasis and leukocytes. Free radical mediated lipid peroxidation and COX-mediated inflammation correlated to cytokine expression and organ dysfunction in endotoxaemic shock. Endotoxaemic pigs pretreated with clopidogrel, exhibited a trend towards less expressed deterioration of renal function, although blocking of ADP-induced primary haemostasis is not a key mediator of endotoxin induced deterioration of renal function. Tobramycin did not neutralise the biological effects of endotoxin or the plasma levels of endotoxin, suggesting that these antibiotics do not bind to endotoxin. Reduction in IL-6 was greater in pigs treated with ceftazidime and tobramycin as compared with those given saline, indicating a possible anti-inflammatory effect of both antibiotics.

Der Sinn ungerichteter Reihenuntersuchungen, sogenannter Screening-untersuchungen, als Ergänzung zur präanästhetischen Untersuchung wird sowohl in Human- als auch Veterinärmedizin kontrovers diskutiert. Ziel dieser Arbeit war es, den Nutzen von Blutuntersuchungen beim Hund im Sinne eines ungerichteten Screenings zu prüfen. Bei 1537 Hunden wurde im Routinebetrieb der Klinik vor jeder Narkose zunächst eine standardisierte Anamnese erhoben und eine standardisierte klinische Untersu-chung durchgeführt. Im Anschluss hieran wurden Blutproben für die Untersuchung verschiedener Parameter des Blutbildes und der Blutchemie entnommen. 1123 Pati-enten wurden präanästhetisch vom Anästhesisten als „benötigt keine Laboruntersu-chung“ eingestuft. Diese Patientengruppe hätte ein ungerichtetes präanästhetisches Laborscreening betroffen und wurde für die Auswertung der Blutuntersuchung herangezogen. Der Anteile der Werte, die außerhalb des jeweiligen Referenzbereichs lagen, schwankte je nach Parameter zwischen 2 und 85 Prozent. Insgesamt wurden für die einzelnen Parameter deutlich mehr Abweichungen festgestellt als in vergleichbaren humanmedizinischen Studien. Der Anteil geringgradiger Abweichungen war hierbei sehr hoch. Aufregungsbedingte Blutbildveränderungen, Vorbehandlungen, der verwendete Referenzbereich und bei sehr jungen Hunden altersbedingte Abweichungen kamen als mögliche Ursachen für diese Veränderungen in Betracht. In elf Prozent der Fälle ließen sich deutliche Abweichungen einzelner Laborparameter vom Referenzbereich feststellen, die retrospektiv zu einer Neueinschätzung des jeweiligen Narkoserisikos beim Patienten führten. Hieraus hätte sich für 6,5 % aller Patienten eine Änderung im perioperativen Management ergeben. In humanmedizinischen Studien liegt der Anteil der Patienten, bei denen ein Laborscreening eine Änderung des Narkosemanagements ergeben hätte bei unter einem Prozent. Verschiedene spezifisch veterinärmedizinische Gründe werden für diese Diskrepanz vermutet. Aufgrund der Besitzeranamnese statt Patientenanamnese und aufgrund verschiedener Störfaktoren für die klinische Untersuchung wie Aufregung oder mangelnde Kooperationsbereitschaft des Patienten kann von einem höheren Prozentsatz nicht erfasster Patienten mit höhe-rem Narkoserisiko ausgegangen werden. Bezüglich aller untersuchten Patienten konnte ein deutlicher Einfluss des Alters auf die Risikoeinschätzung des Anästhesisten festgestellt werden. Eine Untersuchung auf Korrelationen zwischen Laborwerten und dem Alter der Tiere zeigte im Falle von Thrombozytenzahl, ALAT, Natriumkonzentration und Gesamteiweißkonzentration eine positive Korrelation zum Alter, im Falle der Glukose eine negative Korrelation. Der Einfluss des Alters auf die Laborparameter ist aber in allen Fällen zu gering ausgeprägt um für die Beurteilung der Laborparameter hinsichtlich einer Narkoserelevanz entscheidend zu sein. Die Altersstruktur der „laborauffälligen“ Patienten weist im Vergleich zu den „laborunauffälligen“ Patienten keinen statistisch sicherbaren Unterschied auf. Der Einfluss verschiedener Rassen auf die Variabilität der Laborparameter wurde anhand der Korrelation von Körpermasse und Laborparametern näherungsweise untersucht. Nur für Kreatinin konnte ein deutlicher Zusammenhang zwischen Kör-permasse und Laborwert festgestellt werden, was wahrscheinlich auf die unter-schiedliche Bemuskelung kleiner und großer Hunde, bezogen auf das Körperge-wicht, zurückzuführen ist. Für die Laborwertinterpretation relevante rassebedingte Unterschiede konnten jedoch nicht ausgemacht werden. Zusammenfassend zeigen die Ergebnisse dieser Studie deutliche Unterschiede zu denen vergleichbarer Humanmedizinischer Studien. Es können mittels eines unge-richteten Laborscreenings deutlich mehr relevante Laborwertveränderungen festge-stellt werden, die auch zu einer Neueinschätzung der Risikosituation für den Patienten führen können. Ein Einfluss des Alters auf die Zahl der Laborwertveränderungen konnte im Rahmen dieser Studie nicht festgestellt bzw. statistisch gesichert werden. Insgesamt zeigt der Anteil relevanter Laborwertveränderungen, dass präanästhetische Blutuntersuchungen beim Hund eine sinnvolle Ergänzung zur präanästhetischen Untersuchung darstellen können.

A need for the personnel at the Anaesthesiology and Intensive Care Unit at Danderyd Hospital to better understand their patients’ experiences and attitudes towards participation in their care was identified by the Clinical Innovation Fellowship program at Centre for Technology in Medicine and Health. This study aimed to provide the Anaesthesiology and Intensive Care Unit with information on patients and personnel’s experiences and attitudes towards patients’ participation; this would allow them to understand how they should focus their resources. A crosssectional and group comparing survey was performed at the Anaesthesiology and Intensive Care Unit in the spring of 2016. A total of 55 patients scheduled for surgery and 38 from the personnel at the Anaesthesiology and Intensive Care Unit participated. The results show there is high overall satisfaction among the participants of their experiences of patients’ participation. The majority of the patients wanted to be passive in decisions, no connections between personal characteristics and preferred level of participation was found. Patients who did not felt they had been able to participate enough also felt uninformed. Furthermore, physicians seemed to have better opportunities to include patients in decisions compared to the nurses. The healthcare systems should work to adapt the care for each individual patient and to provide them with information suitable for the individual in order to support patients’ participation; IT-systems could be one way of doing this. Future studies should further investigate which factors could influence patients’ participation and how healthcare services and technology could be designed in order to support patient participation. / Clinical Innovation Fellowship programmet från Centrum för teknik i medicin och hälsa identifierade ett behov hos personalen på Anestesi- och intensivvården på Danderyds sjukhus att bättre förstå vad deras patienter hade för förväntningar på sin medverkan i vården. Detta examensarbete syftar till att ge Anestesi- och intensivvården information om patienters och personals erfarenheter och förväntningar på patienters medverkan i vården för att de ska veta var de ska fokusera sina resurser. En enkätstudie har genomförts på Anestesi- och intensivvården under våren 2016. Totalt deltog 55 patienter som var inplanerade på operation samt 38 personer ur personalen på Anestesi- och intensivvården. Resultaten visar att majoriteten överlag är nöjda med sina erfarenheter gällande patienters medverkan. Majoriteten av patienterna vill ha en passiv roll i besluten, det var inte möjligt att identifiera karaktärsdrag bland de olika patientgrupperna för önskad beslutsnivå. Patienter som kände att de inte hade deltagit tillräckligt mycket kände även att de inte fått tillräckligt med information. Vidare kände läkare i större utsträckning än sjuksköterskor att de hade möjligheten att inkludera patienterna i besluten. Sjukvården borde sträva efter att anpassa vården utifrån individen och erbjuda patienter information som är bäst lämpad för dem, ett sätt att erbjuda information kan vara med hjälp av IT-system. Framtida studier borde undersöka vilka faktorer som influerar patienters medverkan samt undersöka hur tjänster och teknik inom vården bäst kan utformas för att stödja patienternas medverkan.

Objective:Iatrogenic acute limb ischaemia in paediatric patients is a well-recognised complication of vascular access. This retrospective review of a paediatric intensive care unit identified patients who developed iatrogenic acute limb ischaemia between January 2008 and July 2013. Methods: The medical records of inpatients diagnosed with acute limb ischaemia during the study period were reviewed. Patients with other causes of acute limb ischaemia were excluded. A descriptive analysis of demographics, primary diagnosis, type of vascular access used, affected anatomical region, clinical presentation, type of therapy, type of block, response to intervention used and outcomes was conducted. Results:A total of 28 patients presented with signs of acute limb ischaemia, of whom 28.6% were aged <30 days, 46.4 % were between one and 12 months and 25% were between one and five years old; 78.6% of the affected limbs were lower limbs. Four patients had resolution of ischaemia upon removal of the vascular access devices. 23 patients received various forms of pharmacological sympathectomy, in addition to conservative therapy. One patient had missing data on the type of sympathectomy that was done. The response to the sympathectomies was: 60.9% good, 8.7% moderate, 8.7% poor and in 21.7% no responses. Documented tissue loss related to the ischaemia occurred in six (21.4%) of the 28 patients. Conclusions: Iatrogenic acute limb ischaemia in children are usually managed without surgical intervention. Pharmacological sympathectomies lead to increased blood flow to the affected limb via vasodilatation of collateral vessels, with an added advantage of reducing ischemic pain. The improved blood flow is postulated to avoid and/or minimise the amount of tissue loss. Pharmacological sympathectomies may, thus, have a role to play in th e management of iatrogenic acute limb ischaemia in the paediatric population.

Thesis (MMed)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: BACKGROUND Post anesthesia discharge criteria scoring systems have been used successfully to aid discharge from the post anesthetic care unit (PACU) for over 40 years. They do not replace, but rather act in conjunction with good clinical judgment, and provide concise, standardized documentation of a patient’s readiness for discharge. 1,2,3,4,5 In order to improve patient safety, provide clear documentation and to aid future audit, a discharge criteria scoring system was developed for use in our PACU (Addendum A). It is a modification of the Aldrete Scoring System and the modified Post Anesthetic Discharge Scoring System (PADSS) proposed by Chung.1 There is a steadily increasing patient burden on the existing medical infrastructure in South Africa. Tygerberg Academic Hospital is no exception, and because of the high demand on our theatre services, optimal efficiency is essential. We speculated that our discharge criteria scoring system might increase the efficiency of our PACU when compared to the traditional time based system. The more healthy patients, undergoing minor procedures, could potentially spend less time in PACU, allowing the nurses to focus on problem cases. Increasing the speed of transit might also help prevent delays in theatre due to lack of bed space in PACU. Our primary endpoint was to compare the duration of time spent by patients in the PACU at Tygerberg Academic Hospital, from the moment they are admitted, to the time they are discharged to the ward, before and after the introduction of a discharge criteria scoring system. While planning the audit, one of the factors that staff identified as contributing to delayed discharge from PACU, was the time it took for the wards to collect their patients. A secondary objective, therefore, was to assess the amount of time that elapsed between calling the ward to collect the patient, and the patient leaving PACU. METHODS AND MATERIALS Prior to commencing the audit, approval was obtained from the Human Research Ethics Committee of the Faculty of Health Sciences of the University of Stellenbosch and Tygerberg Academic Hospital. The Audit, its purpose and possible benefits, was discussed with representatives of the nurses working in PACU, and written consent was obtained from those who would be involved in the data collection (Addendum B). Audit forms (Addendum C), collection boxes, and posters reminding staff to participate in the audit were prepared. Our first audit was performed over approximately a week in August 2012. During this period, the traditional time-based discharge system was still in operation. Data was captured from 327 patients. Audit forms were placed in a collection box, which was cleared daily by the primary investigator. The discharge criteria scoring system was introduced to the PACU staff in January 2013. The nurses were trained in its use, and a one month period was allowed for all involved to become accustomed to the new system. A second audit was performed in February 2013, again over a week, during which we gathered data from 313 patients. RESULTS The median value of the time spent by patients in the PACU decreased from 1 hour 25 minutes, to 1 hour 15 minutes, after introduction of the discharge criteria scoring system. This was statistically significant (p-value = 0.003). The median time between calling the ward to collect a patient, and the patient leaving recovery, was 15 minutes. CONCLUSION The main finding of the study was that the introduction of a discharge criteria scoring system decreased the median duration of time spent by patients in the post anesthetic care unit at Tygerberg Academic Hospital. / AFRIKAANSE OPSOMMING: AGTERGROND Puntestelsels as ontslag kriteria na narkose, word vir die afgelope 40 jaar suksesvol gebruik as maatstaf om pasiënte uit die herstelkamer te ontslaan. Hierdie kriteria vervang nie goeie kliniese oordeel nie, maar is ’n addisionele hulpmiddel om te bepaal of die pasiënt gereed is vir ontslag en om noukeurige, gestandardiseerde dokumentasie te verseker. 1,2,3,4,5 'n Nuwe puntestelsel vir ontslag is vir die herstelkamer van Tygerberg Akademiese Hospitaal ontwikkel om pasiëntesorg en dokumentasie te verbeter, asook om ouditering in die toekoms te vergemaklik (Addendum A). Hiervoor is die Aldrete Scoring System en die gemodifiseerde PADSS, voorgestel deur Chung, aangepas. 1 Die bestaande mediese infrastruktuur in Suid-Afrika beleef tans ‘n geleidelike toename in die getal pasiënte. Tygerberg Akademiese Hospitaal is geen uitsondering nie en as gevolg van die hoë aanvraag na ons teaterdienste, is uiterste doeltreffendheid noodsaaklik. Ons vermoede was dat hierdie aangepaste puntestelsel doeltreffendheid in die herstelkamer sou verbeter in vergelyking met die meer tradisionele tyd-gebaseerde sisteem. Gesonde pasiënte wat kleiner prosedures ondergaan, sal waarskynlik na ’n korter periode ontslaan kan word wat die verpleegpersoneel in staat sal stel om meer aandag aan probleem gevalle te gee. Bespoediging van die pasiëntvloei behoort onnodige vertragings van teatergevalle weens 'n tekort aan beddens in die herstelkamer, te beperk. Die primêre doel van die studie was om te bepaal of die gebruik van die aangepaste puntestelsel as ontslag kriteria in Tygerberg Akademiese Hospitaal, die tydperk wat die pasiënt in die herstelkamer deurbring, verkort. Die herstelkamer verpleegsters het beweer dat die saal personeel ‘n lang tyd gevat het om hulle pasiente in herstelkamer te kom haal. Vervolgens is 'n sekondêre doelwit ingesluit om die tydperk te bepaal vandat die saalpersoneel in kennis gestel word, totdat die pasiënt die herstelkamer verlaat. METODE Goedkeuring is verkry van die Menslike Navorsing en Etiese Komitee van die Gesondheidswetenskap Fakulteit van die Universiteit van Stellenbosch en Tygerberg Akademiese Hospitaal voor die aanvang van die studie. Die studie, asook die doel en moontlike voordele daarvan is vooraf bepsreek met verteenwoordigers van die herstelkamer verpleegpersoneel en skriftelike toestemming is verkry van al die deelnemers wat betrokke sou wees by die data versameling (Addendum B). Oudit vorms (Addendum C), versamelhouers en inligtingsplakkate vir die betrokke personeel is voorberei. Die aanvanklike oudit is in Augustus 2012 oor 'n periode van ongeveer een week uitgevoer. Tydens hierdie oudit is die tradisionele tydgebaseerde sisteem gebruik. Inligting van 327 pasiёnte is versamel. Die oudit vorms is in die versamelbokse geplaas en is daagliks deur die primêre navorser verwyder. Die aangepaste puntestelsel as ontslag kriteria, is in Januarie 2013 in die herstelkamer geïmplementeer. Die verpleegpersoneel het opleiding ontvang waarna die aangepaste puntestelsel vir een maand gebruik is om te verseker dat die personeel vertroud is daarmee. In Februarie 2013, is ‘n tweede oudit oor ‘n tydperk van een week uitgevoer, waartydens inligting van 313 pasiёnte versamel is. RESULTATE Na die implementering van die aangepaste puntestelsel as ontslag kriteria, het die mediane tyd wat pasiënte in die herstelkamer deurbring afgeneem van 1 uur en 25 minute tot 1 uur en 15 minute. Hierdie afname is statities betekenisvol (p-waarde = 0.003) Die mediane tyd vandat die saal in kennis gestel is totdat die pasiënt die herstelkamer verlaat, was 15 minute. GEVOLGTREKKING Die hoof bevinding van die studie is dat die mediane tydperk wat die pasiënte in die herstelkamer deurbring verminder is deur die implementering van die aangepaste puntestelsel as ontslag kriteria in Tygerberg Akademiese Hospitaal.

Introduction: The dissertation of "The concept of basal stimulation from the point view of nurses working on Anaesthesiology and Resuscitation facility", discusses the matters of specifics and issues when it comes to providing a basal stimulation process within patient's hospitalization in a resuscitation unit. Patients in very complicated health conditions are hospitalized in a resuscitation unit, very often with symptoms of impaired consciousness. The concept of basal stimulation could very likely help patients' communication with other environment, with accepting and perceiving the actual situation as well as with recovering itself. The point of this dissertation is to chart the real and actual problematics of the basal stimulation used within resuscitation units, and also how nurses working in these units are bringing the concept to bear within their practice. Research methods and results: There are qualitative results posted within the empiric part of the research, as well as interviews with ten general educated nurses working in a resuscitation unit. All the results are collated and analysed in the final discussion after literal transcription of all the interviews. The result of which is, that the general educated nurses see the biggest issue when it comes to providing a basal stimulation...

Ovariohysterectomy and castration are common surgical procedures in small animal practice that can result in clinically significant postoperative pain. One way of controlling postoperative pain is administration of a single analgesic or a combination of different classes of analgesics prior to the onset of noxious stimuli. A constraint to the perioperative use of traditional opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is their undesirable side effects. In this series of experiments, the preventive (pre-emptive) analgesic efficacy of two popular human analgesics, tramadol (an ?atypical? opioid) and parecoxib (a NSAID with selective COX-2 inhibition) was evaluated in dogs. Initially, the efficacy and renal safety of parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol (a -adrenoceptor blocker and 5-HT1A/1B antagonist) were screened in anaesthetised healthy dogs. These analgesics increased the dogs? nociceptive threshold to mechanical stimuli, without causing significant alterations in the dogs? glomerular filtration rate (GFR) estimated by plasma iohexol clearance. Subsequently, the efficacy of tramadol was compared with morphine, in dogs undergoing ovariohysterectomy or castration. The Glasgow composite measure pain scale-short form score (CMPS-SF) and changes in intraoperative electroencephalogram (EEG) responses were used to assess the efficacy of analgesics. Of the three treatment groups (preoperative morphine, 0.5 mg kg-1; preoperative tramadol, 3 mg kg-1; a ?combination? of preoperative low-dose morphine, 0.1 mg kg-1, and postoperative tramadol 3 mg kg-1), dogs given the ?combination? had significantly lower pain scores after ovariohysterectomy. In castrated dogs, preoperative tramadol (3 mg kg-1) and morphine (0.5 mg kg-1) were tested and no significant difference in the CMPS-SF score were observed between them. Changes in EEG variables were not specific between the treatment groups in ovariohysterectomised dogs. Finally, the efficacy of test drugs was evaluated against acute noxious electrical stimulation in anaesthetised dogs, using EEG. Median frequency of the EEG, a reliable indicator of nociception, increased significantly in tramadol and parecoxib groups, compared to morphine, after electrical stimulation. These studies demonstrated that tramadol and parecoxib can produce analgesia in dogs with insignificant side effects. The efficacy of tramadol appears to vary with the type of noxious stimulus. A complete prevention of noxious input by administration of analgesics pre- and post-operatively could have important clinical applications.

Ovariohysterectomy and castration are common surgical procedures in small animal practice that can result in clinically significant postoperative pain. One way of controlling postoperative pain is administration of a single analgesic or a combination of different classes of analgesics prior to the onset of noxious stimuli. A constraint to the perioperative use of traditional opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is their undesirable side effects. In this series of experiments, the preventive (pre-emptive) analgesic efficacy of two popular human analgesics, tramadol (an ?atypical? opioid) and parecoxib (a NSAID with selective COX-2 inhibition) was evaluated in dogs. Initially, the efficacy and renal safety of parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol (a -adrenoceptor blocker and 5-HT1A/1B antagonist) were screened in anaesthetised healthy dogs. These analgesics increased the dogs? nociceptive threshold to mechanical stimuli, without causing significant alterations in the dogs? glomerular filtration rate (GFR) estimated by plasma iohexol clearance. Subsequently, the efficacy of tramadol was compared with morphine, in dogs undergoing ovariohysterectomy or castration. The Glasgow composite measure pain scale-short form score (CMPS-SF) and changes in intraoperative electroencephalogram (EEG) responses were used to assess the efficacy of analgesics. Of the three treatment groups (preoperative morphine, 0.5 mg kg-1; preoperative tramadol, 3 mg kg-1; a ?combination? of preoperative low-dose morphine, 0.1 mg kg-1, and postoperative tramadol 3 mg kg-1), dogs given the ?combination? had significantly lower pain scores after ovariohysterectomy. In castrated dogs, preoperative tramadol (3 mg kg-1) and morphine (0.5 mg kg-1) were tested and no significant difference in the CMPS-SF score were observed between them. Changes in EEG variables were not specific between the treatment groups in ovariohysterectomised dogs. Finally, the efficacy of test drugs was evaluated against acute noxious electrical stimulation in anaesthetised dogs, using EEG. Median frequency of the EEG, a reliable indicator of nociception, increased significantly in tramadol and parecoxib groups, compared to morphine, after electrical stimulation. These studies demonstrated that tramadol and parecoxib can produce analgesia in dogs with insignificant side effects. The efficacy of tramadol appears to vary with the type of noxious stimulus. A complete prevention of noxious input by administration of analgesics pre- and post-operatively could have important clinical applications.