Clinical Studies on Epidural and Spinal Postoperative Analgesia : With Special Reference to Continuous Techniques of Administration and Adjuvant Drugs

Continuous epidural analgesia (CEA) and continuous spinal postoperative analgesia (CSPA) provided by a mixture of local anaesthetic and opioid are widely used for postoperative pain relief. E.g., with the introduction of so-called microcatheters, CSPA found its way particularly in orthopaedic surgery. These techniques, however, may be associated with dose-dependent side-effects as hypotension, weakness in the legs, and nausea and vomiting. At times, they may fail to offer sufficient analgesia, e.g., because of a misplaced catheter. The correct position of an epidural catheter might be confirmed by the supposedly easy and reliable epidural stimulation test (EST). The aims of this thesis were to determine a) whether the efficacy, tolerability, and reliability of CEA might be improved by adding the α2-adrenergic agonists adrenaline and clonidine to CEA, and by the repeated use of EST during CEA; and, b) the feasibility of CSPA given through a microcatheter after vascular surgery. Studies I IV were double-blinded, randomized, and controlled trials; Study V was of a diagnostic, prospective nature. Patients underwent arterial bypass surgery of the legs (I, n=50; IV, n=46), total knee arthroplasty (II, n=70; III, n=72), and abdominal surgery or thoracotomy (V, n=30). Postoperative lumbar CEA consisted of regular mixtures of ropivacaine and fentanyl either without or with adrenaline (2 µg/ml (I) and 4 µg/ml (II)) and clonidine (2 µg/ml (III)). CSPA (IV) was given through a microcatheter (28G) and contained either ropivacaine (max. 2 mg/h) or a mixture of ropivacaine (max. 1 mg/h) and morphine (max. 8 µg/h). Epidural catheter tip position (V) was evaluated both by EST at the moment of catheter placement and several times during CEA, and by epidurography as reference diagnostic test. CEA and CSPA were administered for 24 or 48 h. Study parameters included pain scores assessed with a visual analogue scale, requirements of rescue pain medication, vital signs, and side-effects. Adrenaline (I and II) had no beneficial influence as regards the efficacy or tolerability of CEA. The total amounts of epidurally-infused drugs were even increased in the adrenaline group in Study II (p=0.02, RM ANOVA). Clonidine (III) augmented pain relief with lowered amounts of epidurally infused drugs (p=0.01, RM ANOVA) and reduced need for rescue oxycodone given i.m. (p=0.027, MW-U; median difference 3 mg (95% CI 0 7 mg)). Clonidine did not contribute to sedation and its influence on haemodynamics was minimal. CSPA (IV) provided satisfactory pain relief with only limited blockade of the legs (no inter-group differences). EST (V) was often related to technical problems and difficulties of interpretation, e.g., it failed to identify the four patients whose catheters were outside the spinal canal already at the time of catheter placement. As adjuvants to lumbar CEA, clonidine only slightly improved pain relief, while adrenaline did not provide any benefit. The role of EST applied at the time of epidural catheter placement or repeatedly during CEA remains open. The microcatheter CSPA technique appeared effective and reliable, but needs to be compared to routine CEA after peripheral arterial bypass surgery.

Day Surgery in Finland : randomized and cross-sectional studies on treatment, quality, and outcome

The aims of this study were to describe Finnish day surgery practice at present and to evaluate quality of care by assessing postdischarge minor morbidity and quality indicators. Potential treatment options were approached by investigating the role of oral dexamethasone as a part of multimodal analgesia and the feasibility of day surgery in patients aged 65 years and older. Over a 2-month period, all patient cases at 14 Finnish day surgery or short-stay units were analyzed (Study I). Quality indicators included rates and reasons for overnight admission, readmission, reoperation, cancellations, and patient satisfaction. Recovery during the first postoperative week was assessed at two units (Study II). Altogether 2732 patients graded daily the intensity of predefined symptoms. To define risk factors of postdischarge symptoms, multinomial regression analysis was used. Sixty patients scheduled to undergo day surgery for hallux valgus were randomized to receive twice perioperatively dexamethasone 9 mg or placebo (Study III). Paracetamol 1 g was administered 3 times daily. Rescue medication (oxycodone) consumption during 0-3 postoperative days (POD), maximal pain scores and adverse effects were documented. Medically stable patients aged 65 years or older, scheduled for open inguinal hernia repair, were randomized to receive treatment either as day cases or inpatients (Study IV). Complications, unplanned admissions, healthcare visits, and patients’ acceptance of the type of care provided were assessed during 2 weeks postoperatively. In Study I, unplanned overnight admissions were reported in 5.9%, return hospital visits during PODs 1-28 in 3.7%, and readmissions in 0.7% of patients. Patient satisfaction was high. In Study II, pain was the most common symptom in adult patients (57%). Postdischarge symptoms were more frequent in adults aged < 40 years, children aged ≥ 7 years, females, and following a longer duration of surgery. In Study III, the total median (range) oxycodone consumption during the study period was 45 (0–165) mg in the dexamethasone group, compared with 78 (15–175) mg in the placebo group (P < 0.049). On PODs 0-1, patients in the dexamethasone group reported significantly lower pain scores. Following inguinal hernia repair, no significant differences in outcome measures were seen between the study groups. Patient satisfaction was equally high in day cases and inpatients (Study IV). Finnish day surgery units provide good-quality services. Minor postdischarge symptoms are common, and they are influenced by several patient-, surgery-, and anesthesia-related factors. Oral dexamethasone combined with paracetamol improves pain relief and reduces the need for oxycodone rescue medication following correction of hallux valgus. Day surgery for open inguinal hernia repair is safe and well accepted by patients aged 65 years or older and can be recommended as the primary choice of care for medically stable patients.

Studies on the assessment of the adequacy of anesthesia

Several hypnosis monitoring systems based on the processed electroencephalogram (EEG) have been developed for use during general anesthesia. The assessment of the analgesic component (antinociception) of general anesthesia is an emerging field of research. This study investigated the interaction of hypnosis and antinociception, the association of several physiological variables with the degree of intraoperative nociception, and aspects of EEG Bispectral Index Scale (BIS) monitoring during general anesthesia. In addition, EEG features and heart rate (HR) responses during desflurane and sevoflurane anesthesia were compared. A propofol bolus of 0.7 mg/kg was more effective than an alfentanil bolus of 0.5 mg in preventing the recurrence of movement responses during uterine dilatation and curettage (D C) after a propofol-alfentanil induction, combined with nitrous oxide (N2O). HR and several HR variability-, frontal electromyography (fEMG)-, pulse plethysmography (PPG)-, and EEG-derived variables were associated with surgery-induced movement responses. Movers were discriminated from non-movers mostly by the post-stimulus values per se or normalized with respect to the pre-stimulus values. In logistic regression analysis, the best classification performance was achieved with the combination of normalized fEMG power and HR during D C (overall accuracy 81%, sensitivity 53%, specificity 95%), and with the combination of normalized fEMG-related response entropy, electrocardiography (ECG) R-to-R interval (RRI), and PPG dicrotic notch amplitude during sevoflurane anesthesia (overall accuracy 96%, sensitivity 90%, specificity 100%). ECG electrode impedances after alcohol swab skin pretreatment alone were higher than impedances of designated EEG electrodes. The BIS values registered with ECG electrodes were higher than those registered simultaneously with EEG electrodes. No significant difference in the time to home-readiness after isoflurane-N2O or sevoflurane-N2O anesthesia was found, when the administration of the volatile agent was guided by BIS monitoring. All other early and intermediate recovery parameters were also similar. Transient epileptiform EEG activity was detected in eight of 15 sevoflurane patients during a rapid increase in the inspired volatile concentration, and in none of the 16 desflurane patients. The observed transient EEG changes did not adversely affect the recovery of the patients. Following the rapid increase in the inhaled desflurane concentration, HR increased transiently, reaching its maximum in two minutes. In the sevoflurane group, the increase was slower and more subtle. In conclusion, desflurane may be a safer volatile agent than sevoflurane in patients with a lowered seizure threshold. The tachycardia induced by a rapid increase in the inspired desflurane concentration may present a risk for patients with heart disease. Designated EEG electrodes may be superior to ECG electrodes in EEG BIS monitoring. When the administration of isoflurane or sevoflurane is adjusted to maintain BIS values at 50-60 in healthy ambulatory surgery patients, the speed and quality of recovery are similar after both isoflurane-N2O and sevoflurane-N2O anesthesia. When anesthesia is maintained by the inhalation of N2O and bolus doses of propofol and alfentanil in healthy unparalyzed patients, movement responses may be best avoided by ensuring a relatively deep hypnotic level with propofol. HR/RRI, fEMG, and PPG dicrotic notch amplitude are potential indicators of nociception during anesthesia, but their performance needs to be validated in future studies. Combining information from different sources may improve the discrimination of the level of nociception.

Total Hip and Knee Arthoplasty for Osteoarthritis : Factors Related to the Early Outcome of Surgery

Some perioperative clinical factors related to the primary cemented arthroplasty operation for osteoarthritis of the hip or knee joint are studied and discussed in this thesis. In a randomized, double-blind study, 39 patients were divided into two groups: one receiving tranexamic acid and the other not receiving it. Tranexamic acid was given in a dose of 10 mg/kg before the operation and twice thereafter, at 8-hour intervals. Total blood loss was smaller in the tranexamic acid group than in the control group. No thromboembolic complications were noticed. In a prospective, randomized study, 58 patients with hip arthroplasty and 39 patients with knee arthroplasty were divided into groups with postoperative closed-suction drainage and without drainage. There was no difference in healing of the wounds, postoperative blood transfusions, complications or range of motion. As a result of this study, the use of drains is no longer recommended. In a randomised study the effectiveness of a femoral nerve block (25 patients) was compared with other methods of pain control (24 patients) on the first postoperative day after total knee arthroplasty. The femoral block consisted of a single injection administered at patients´ bedside during the surgeon´s hospital rounds. Femoral block patients reported less pain and required half of the amount of oxycodone. Additional femoral block or continued epidural analgesia was required more frequently by the control group patients. Pain management with femoral blocks resulted in less work for nursing staff. In a retrospective study of 422 total hip and knee arthroplasty cases the C-reactive protein levels and clinical course were examined. After hip and knee arthroplasty the maximal C-reactive protein values are seen on the second and third postoperative days, after which the level decreases rapidly. There is no difference between patients with cemented or uncemented prostheses. Major postoperative complications may cause a further increase in C-reactive protein levels at one and two weeks. In-hospital and outpatient postoperative control radiographs of 200 hip and knee arthroplasties were reviewed retrospectively. If postoperative radiographs are of good quality, there seems to be no need for early repetitive radiographs. The quality and safety of follow-up is not compromised by limiting follow-up radiographs to those with clinical indications. Exposure of the patients and the staff to radiation is reduced. Reading of the radiographs by only the treating orthopaedic surgeon is enough. These factors may seem separate from each other, but linking them together may help the treating orthopaedic surgeon to adequate patient care strategy. Notable savings can be achieved.

Detection of renal dysfunction during and after anaesthesia and surgery - evaluation of the influence of inorganic fluoride, ketorolac and clonidine

Drugs and surgical techniques may have harmful renal effects during the perioperative period. Traditional biomarkers are often insensitive to minor renal changes, but novel biomarkers may more accurately detect disturbances in glomerular and tubular function and integrity. The purpose of this study was first, to evaluate the renal effects of ketorolac and clonidine during inhalation anesthesia with sevoflurane and isoflurane, and secondly, to evaluate the effect of tobacco smoking on the production of inorganic fluoride (F-) following enflurane and sevoflurane anesthesia as well as to determine the effect of F- on renal function and cellular integrity in surgical patients. A total of 143 patients undergoing either conventional (n = 75) or endoscopic (n = 68) inpatient surgery were enrolled in four studies. The ketorolac and clonidine studies were prospective, randomized, placebo controlled and double-blinded, while the cigarette smoking studies were prospective cohort studies with two parallel groups. As a sign of proximal tubular deterioration, a similar transient increase in urine N-acetyl-beta-D-glucosaminidase/creatinine (U-NAG/crea) was noted in both the ketorolac group and in the controls (baseline vs. at two hours of anesthesia, p = 0.015) with a 3.3 minimum alveolar concentration hour sevoflurane anesthesia. Uncorrelated U-NAG increased above the maximum concentration measured from healthy volunteers (6.1 units/l) in 5/15 patients with ketorolac and in none of the controls (p = 0.042). As a sign of proximal tubular deterioration, U-glutathione transferase-alpha/crea (U-GST-alpha/crea) increased in both groups at two hours after anesthesia but a more significant increase was noted in the patients with ketorolac. U-GST-alpha/crea increased above the maximum ratio measured from healthy volunteers in 7/15 patients with ketorolac and in 3/15 controls. Clonidine diminished the activation of the renin-angiotensin aldosterone system during pneumoperitoneum; urine output was better preserved in the patients treated with clonidine (1/15 patients developed oliguria) than in the controls (8/15 developed oliguria (p=0.005)). Most patients with pneumoperitoneum and isoflurane anesthesia developed a transient proximal tubular deterioration, as U-NAG increased above 6.1 units/L in 11/15 patients with clonidine and in 7/15 controls. In the patients receiving clonidine treatment, the median of U-NAG/crea was higher than in the controls at 60 minutes of pneumoperitoneum (p = 0.01), suggesting that clonidine seems to worsen proximal tubular deterioration. Smoking induced the metabolism of enflurane, but the renal function remained intact in both the smokers and the non-smokers with enflurane anesthesia. On the contrary, smoking did not induce sevoflurane metabolism, but glomerular function decreased in 4/25 non-smokers and in 7/25 smokers with sevoflurane anesthesia. All five patients with S-F- ≥ 40 micromol/L, but only 6/45 with S-F- less than 40 micromol/L (p = 0.001), developed a S-tumor associated trypsin inhibitor concentration above 3 nmol/L as a sign of glomerular dysfunction. As a sign of proximal tubulus deterioration, U-beta 2-microglobulin increased in 2/5 patients with S-F- over 40 micromol/L compared to 2/45 patients with the highest S-F- less than 40 micromol/L (p = 0.005). To conclude, sevoflurane anesthesia may cause a transient proximal tubular deterioration which may be worsened by a co-administration of ketorolac. Clonidine premedication prevents the activation of the renin-angiotensin aldosterone system and preserves normal urine output, but may be harmful for proximal tubules during pneumoperitoneum. Smoking induces the metabolism of enflurane but not that of sevoflurane. Serum F- of 40 micromol/L or higher may induce glomerular dysfunction and proximal tubulus deterioration in patients with sevoflurane anesthesia. The novel renal biomarkers warrant further studies in order to establish reference values for surgical patients having inhalation anesthesia.

Koiran suurimpien nivelten artroskopia ja artroskopialla hoidettavat sairaudet - kirjallisuuskatsaus

Lemmikinomistajien hoitomyönteisyys ja eläinten hyvinvoinnista huolehtiminen, sekä potilasmäärien kasvu onmahdollistanut nivelsairauksien eri hoitomuotojen tutkimuksen ja kehityksen. Kirurgisia hoitoja on kehitetty entisestäänja artroskopia, eli nivelen tähystys, on yleistynyt nivelsairauksien diagnostiikassa ja hoidossa. Artroskopiallavoidaan hoitaa nykytekniikan avulla myös pieniä koiria ja pienempiä niveliä. Artroskopiaa voidaan käyttää epäiltäessä nivelsairautta kliinisten tai röntgenologisten löydösten perusteella. Nivelsairaudenkliinisiä oireita ovat ontuminen, kipu, nivelkapselin laajeneminen, nivelen turvotus, nivelen krepitaatioeli rahina, nivelen löysyys sekä nivelen paksuneminen. Röntgenologisia löydöksiä ovat lisääntynyt nivelneste,nivelkapselin paksuuntuminen, luupiikkien muodostuminen, niveltilan kapeneminen ja nivelen osittainen sijoiltaanmeno.Tähystyksellä diagnosoitavia ja hoidettavia sairauksia ovat osteokondroosi, nivelkierukoiden vauriot,rappeutumista aiheuttavat nivelsairaudet, synoviitti eli nivelkalvon tai nivelen tulehdus sekä kasvaimet. Lisäksitähystystä voidaan käyttää koepalan ottoon nivelkapselista tai bakteerien aiheuttamien niveltulehdusten huuhteluissa. Tähystyksen etuja ovat tähystimen suurentavasta vaikutuksesta aiheutuva parempi näkyvyys ja lisääntynyt diagnostinentarkkuus. Lisäksi tähystämällä on mahdollista tutkia niveltä varhaisessa vaiheessa, jolloin tarpeeton avausvoidaan välttää, mikäli nivelessä ei olekaan muutoksia. Tähystimen pieni koko mahdollistaa myös pienet viillotleikkausalueelle, jolloin vähemmän hermopäätteitä vahingoittuu ja kudosvauriot ovat vähäisempiä verrattunaavoimeen kirurgiaan. Tämä mahdollistaa operoidun raajan käytön aikaisemmin, mikä osaltaan edesauttaa toipumista.Tähystyksellä saadaan myös lyhennettyä operaatioaikaa, jonka seurauksena anestesia-aika ja sen myötä mm.infektioriski pienenevät. Tähystys onkin erinomainen valinta hoidettaessa useampia niveliä yhtä aikaa. Artroskopian haittapuoleksi voidaan laskea kalliit instrumentit. Tähystyslaitteet ovat myös hyvin herkkiä vahingoittumaan,joten niiden käsittely vaatii suurta huolellisuutta. Aloittelevalle kirurgille tähystysleikkaukset voivat ollahankalia, sillä tähystäminen vaatii hyvää koordinaatiokykyä. Kokemuksen lisääntyminen myös vähentää operaatioaikaahuomattavasti. Tässä kirjallisuuskatsauksessa keskitytään koiran viiden suurimman nivelen (kyynärnivel, olkanivel, lonkkanivel,polvinivel ja kinnernivel) anatomiaan, artroskopiaan ja yleisimpiin artroskopialla hoidettaviin nivelsairauksiin.Tutkielmassa kootaan yhteen tämänhetkinen keskeinen tutkimustieto koiran suurimpien nivelten artroskopiastasekä artroskopialla hoidettavista nivelsairauksista.

Kastraation vaihtoehdot: Immunokastraation vaikutus kasvuun ja rehunkulutukseen

Lähes kaikki karjuporsaat kastroidaan Suomessa ja muualla EU:ssa ensimmäisen elinviikon aikana. Kastraation syynä on ns. karjun haju. Karjun haju on uroksen sukupuolihormonien (etenkin androstenonin ja skatolin) vaikutuksesta aiheutuva epämiellyttävä haju leikkaamattoman karjun lihassa. Kastroimalla estetään androstenonin tuotanto, jolloin lihaan ei muodostu karjun hajua. Kastraatio suoritetaan tavallisesti ilman minkäänlaista kivunlievitystä. Toimenpide on hyvin kivulias ja heikentää eläinten hyvinvointia. Kastraatio heikentää myös porsaiden rehuhyötysuhdetta ja aiheuttaa lihan rasvoittumista. Edellä mainittujen syiden vuoksi porsaiden rutiininomaisesta kastroimisesta pyritään luopumaan lähivuosina. Kirurgisen kastraation korvaajaksi on ehdotettu useita eri menetelmiä. Menetelmät eroavat toisistaan huomattavasti kustannustehokkuuden, käytännöllisyyden ja hyvinvointivaikutuksien osalta. Tutkimuksia vaihtoehtoisista karjunhajun ehkäisymenetelmistä on useita. Sukupuolilajitellun siemennesteen käyttö ja karjunhajun hävittäminen jalostamalla eivät ole vielä toteuttamiskelpoisia vaihtoehtoja. Haisevien karjujen tunnistaminen teuraslinjalta ei ole vielä nykytekniikalla mahdollista ilman liian suurta turhien hylkäyksien määrää. Rauhoitus- ja kivunlievitysmenetelmiä on tutkittu runsaasti. Lisätutkimuksia vaaditaan kuitenkin riittävän edullisen sikalaolosuhteissa helposti toteutettavan menetelmän kehittämiseksi. Huonosti toteutettu anestesia ei paranna porsaiden hyvinvointia. Yksi varteenotettava vaihtoehto on immunokastraatio. Immunokastraatiossa porsaille annetaan injektiona valmistetta, joka estää sukupuolielinten normaalin kehityksen, hormonituotannon ja sitä kautta myös karjun hajua. Immunokastraatio on todettu useissa tutkimuksissa turvalliseksi sioille ja kuluttajille sekä tehokkaaksi karjunhajun ehkäisyssä. Tutkimuksissa on saatu myös viitteitä immunokastraation edullisesta vaikutuksesta porsaiden kasvuun ja rehunkäytön tehokkuuteen. Tässä tutkimuksessa todettiin suomalaisilla lihasioilla immunokastraation pienentävän merkittävästi lihan rasvapitoisuutta leikkoihin verrattuna. Paremmasta rehunkäytön hyötysuhteesta ei saatu tilastollisesti merkitsevää (p<0,05) eroa, mutta asiaa on syytä tutkia tarkemmin. Ennen immunokastraation laajamittaista käyttöä on myös selvitettävä kuluttajien ja sikatilallisten asenteet valmisteen käyttöä kohtaan. Tähänastisten tutkimustulosten valossa immunokastraatiota voidaan pitää hyvin lupaavana vaihtoehtona rutiininomaiselle kirurgiselle kastraatiolle sekä tuotannon taloudellisuuden että eläinten hyvinvoinnin näkökulmasta.