Healthcare-Associated Infections in Pediatrics

Healthcare-associated infections (HAIs) are known to increase the risk for patient morbidity and mortality in different healthcare settings and thereby to cause additional costs. HAIs typically affect patients with severe underlying conditions. HAIs are prevalent also among pediatric patients, but the distribution of the types of infection and the causative agents differ from those detected in adults. The aim of this study was to obtain information on pediatric HAIs in Finland through an assessment of the surveillance of bloodstream infections (BSIs), through two outbreak investigations in a neonatal intensive care unit (NICU), and through a study of postoperative HAIs after open-heart surgery. The studies were carried out at the Hospital for Children and Adolescents of Helsinki University Central Hospital. Epidemiological features of pediatric BSIs were assessed. For the outbreak investigations, case definitions were set and data collected from microbiological and clinical records. The antimicrobial susceptibilities of the Serratia marcescens and the Candida parapsilosis isolates were determined and they were genotyped. Patient charts were reviewed for the case-control and cohort studies during the outbreak investigations, as well as for the patients who acquired surgical site infections (SSIs) after having undergone open-heart surgery. Also a prospective postdischarge study was conducted to detect postoperative HAIs in these patients. During 1999-2006, the overall annual BSI rate was 1.6/1,000 patient days (range by year, 1.2–2.1). High rates (average, 4.9 and 3.2 BSIs/1,000 patient days) were detected in hematology and neonatology units. Coagulase-negative staphylococci were the most common pathogens both hospital-wide and in each patient group. The overall mortality was 5%. The genotyping of the 15 S. marcescens isolates revealed three independent clusters. All of the 26 C. parapsilosis isolates studied proved to be indistinguishable. The NICU was overcrowded during the S. marcescens clusters. A negative correlation between C. parapsilosis BSIs and fluconazole use in the NICU was detected, and the isolates derived from a single initially susceptible strain became less susceptible to fluconazole over time. Eighty postoperative HAIs, including all severe infections, were detected during hospitalization after open-heart surgery; 34% of those HAIs were SSIs and 25% were BSIs. The postdischarge study found 65 infections that were likely to be associated with hospitalization. The majority (89%) of them were viral respiratory or gastrointestinal infections, and these often led to rehospitalizations. The annual hospital-wide BSI rates were stable, and the significant variation detected in some units could not be seen in overall rates. Further studies with data adequately adjusted for risk factors are needed to assess BSI rates in the patient groups with the highest rates (hematology, neonatology). The outbreak investigations showed that horizontal transmission was common in the NICU. Overcrowding and lapses in hand hygiene probably contributed to the spreading of the pathogens. Following long-term use of fluconazole in the NICU, resistance to fluconazole developed in C. parapsilosis. Almost one-fourth of the patients who underwent open-heart surgery acquired at least one HAI. All severe HAIs were detected during hospitalization. The postdischarge study found numerous viral infections, which often caused rehospitalization.

Brain and Spinal Cavernomas : Helsinki Experience

Cavernomas are rare neurovascular lesions, encountered in up to 10% of patients harboring vascular abnormalities of the CNS. Cavernomas consist of dilated thin-walled sinusoids or caverns covered by a single layer of endothelium. Due to advancements in neuroradiology, the number of cavernoma patients coming to be evaluated in neurosurgical practice is increasing. In the present work, we summarized our results on the treatment of cavernomas. Particular attention was paid to uncommon locations or insufficiently investigated cavernomas, including 1. Intraventricular cavernomas; 2. Multiple cavernomas; 3. Spinal cavernomas; and 4. Temporal lobe cavernomas. After analyzing the patient series with these lesions, we concluded that: 1. IVCs are characterized by a high tendency to cause repetitive hemorrhages in a short period of time after the first event. In most patients, hemorrhages were not life-threatening. Surgery is indicated when re-bleedings are frequent and the mass-effect causes progressive neurological deterioration. Modern microsurgical techniques allow safe removal of the IVC, but surgery on fourth ventricle cavernomas carries increased risk of postoperative cranial nerve deficits. 2. In MC cases, when the cavernoma bleeds or generates drug-resistant epilepsy, microsurgical removal of the symptomatic lesion is beneficial to patients. In our series, surgical removal of the most active cavernoma usually the biggest lesion with signs of recent hemorrhage - was safe and prevented further bleedings. Epilepsy outcome showed the effectiveness of active treatment of MCs. However, due to the remaining cavernomas, epileptogenic activity can persist postoperatively, frequently necessitating long-term use of antiepileptic drugs. 3. Spinal cavernomas can cause severe neurological deterioration due to low tolerance of the spinal cord to mass-effect with progressive myelopathy. When aggravated by extralesional massive hemorrhage, neurological decline is usually acute and requires immediate treatment. Microsurgical removal of a cavernoma is effective and safe, improving neurological deficits. Sensorimotor deficits and pain improved postoperatively at a high rate, whereas bladder dysfunction remained essentially unchanged, causing social discomfort to patients. 4. Microsurgical removal of temporal lobe cavernomas is beneficial for patents suffering from drug-resistant epilepsy. In our series, 69% of patients with this condition became seizure-free postoperatively. Duration of epilepsy did not correlate with seizure prognosis. The most frequent disabling symptom at follow-up was memory disorder, considered to be the result of a complex interplay between chronic epilepsy and possible damage to the temporal lobe during surgery.

Thrombin regulation in newborn infants

The coagulation system of newborn infants differs markedly from that of older children and adults. The activities of most coagulation factors and anticoagulants are low, leading to altered regulation in the formation of the key enzyme, thrombin. Timely and adequate generation of thrombin is essential, as thrombin activates platelets and many coagulation factors, cleaves fibrinogen into fibrin and activates the antithrombotic and anti-inflammatory protein C pathway. On the other hand, excess thrombin may promote thrombotic complications and exacerbate harmful inflammatory reactions. Despite the characteristic features, the newborn coagulation system can be considered physiological, since healthy newborns rarely show haemorrhagic or thrombotic complications. Sick newborns, however, often encounter clinical situations that challenge their coagulation system. The aim of this study was to clarify the behaviour of the neonatal coagulation system in selected clinical situations, with a special emphasis on the generation of thrombin. Thrombin was measured by in vivo thrombin generation markers and by thrombin generation potential in vitro. The patient groups included sick newborns undergoing intensive care and receiving fresh-frozen plasma (FFP), requiring exchange transfusions (ET) or presenting with a congenital heart defect requiring open heart surgery. Additionally, healthy newborns with inherited heterozygous factor V Leiden (FVL) mutation were studied. Thrombin generation potential was also analysed in cord plasma of healthy infants and in adults. Healthy as well as sick newborn infants showed lower total thrombin generation potential in vitro but faster initiation of thrombin generation than adults. These findings were qualitatively similar when plasma was supplemented with platelets. Platelets, however, significantly altered the effect of the major anticoagulant, activated protein C (APC), on thrombin generation potential. In accordance with previous studies, thrombin generation in healthy newborn platelet-poor plasma was resistant to the anticoagulant effects of APC, but when the plasma was supplemented with platelets APC attenuated thrombin generation significantly more in newborns than in adults. In vivo generation of thrombin was elevated in nearly all of the sick newborn infants. The low-volume FFP transfusion as opposed to the change from neonatal to adult blood in ET exerted markedly different effects on neonatal thrombin generation. FFP reduced the in vivo generation of thrombin in those newborns with the highest pretransfusional thrombin generation, thus acting as an anticoagulant agent. In those infants with lower pretransfusional thrombin generation, the effect of FFP on thrombin generation was fairly neutral. On the other hand, the combination of red blood cells and FFP, used to perform ET, significantly increased the in vivo thrombin formation and shifted the balance in the newborn coagulation system to the procoagulant direction. Cardiopulmonary bypass (CPB) also significantly increased the in vivo thrombin generation, but the thrombin generation profile during CPB differed from that previously observed in adults. Escalation of thrombin at early reperfusion was not observed in newborns; in adults, its occurrence is associated with postoperative myocardial damage. Finally, in healthy newborns with FVL heterozygosity, faster initiation of thrombin generation was observed compared with controls. Interestingly, FV level was lower in FVL-heterozygous infants, possibly to counteract the procoagulant effects induced by FVL. In conclusion, unique features regarding thrombin regulation in newborn infants were observed. These features included a novel platelet effect on the regulation of the protein C pathway. The clinical challenges mainly seemed to shift the balance in the coagulation system of newborns to the procoagulant direction. Blood component transfusions markedly affected coagulation in a manner specific to the product but that could also be altered by the clinical situation. Overall, the results highlight the need for understanding developmental haemostasis for both diagnostic and therapeutic purposes.

Imaging of knee injuries with special focus on tibial plateau fractures

Acute knee injury is a common event throughout life, and it is usually the result of a traffic accident, simple fall, or twisting injury. Over 90% of patients with acute knee injury undergo radiography. An overlooked fracture or delayed diagnosis can lead to poor patient outcome. The major aim of this thesis was retrospectively to study imaging of knee injury with a special focus on tibial plateau fractures in patients referred to a level-one trauma center. Multi-detector computed tomography (MDCT) findings of acute knee trauma were studied and compared to radiography, as well as whether non-contrast MDCT can detect cruciate ligaments with reasonable accuracy. The prevalence, type, and location of meniscal injuries in magnetic resonance imaging (MRI) were evaluated, particularly in order to assess the prevalence of unstable meniscal tears in acute knee trauma with tibial plateau fractures. The possibility to analyze with conventional MRI the signal appearance of menisci repaired with bioabsorbable arrows was also studied. The postoperative use of MDCT was studied in surgically treated tibial plateau fractures: to establish the frequency and indications of MDCT and to assess the common findings and their clinical impact in a level-one trauma hospital. This thesis focused on MDCT and MRI of knee injuries, and radiographs were analyzed when applica-ble. Radiography constitutes the basis for imaging acute knee injury, but MDCT can yield information beyond the capabilities of radiography. Especially in severely injured patients , sufficient radiographs are often difficult to obtain, and in those patients, radiography is unreliable to rule out fractures. MDCT detected intact cruciate ligaments with good specificity, accuracy, and negative predictive value, but the assessment of torn ligaments was unreliable. A total of 36% (14/39) patients with tibial plateau fracture had an unstable meniscal tear in MRI. When a meniscal tear is properly detected preoperatively, treatment can be combined with primary fracture fixation, thus avoiding another operation. The number of meniscal contusions was high. Awareness of the imaging features of this meniscal abnormality can help radiologists increase specificity by avoiding false-positive findings in meniscal tears. Postoperative menisci treated with bioabsorbable arrows showed no difference, among different signal intensities in MRI, among menisci between patients with operated or intact ACL. The highest incidence of menisci with an increased signal intensity extending to the meniscal surface was in patients whose surgery was within the previous 18 months. The results may indicate that a rather long time is necessary for menisci to heal completely after arrow repair. Whether the menisci with an increased signal intensity extending to the meniscal surface represent improper healing or re-tear, or whether this is just the earlier healing feature in the natural process remains unclear, and further prospective studies are needed to clarify this. Postoperative use of MDCT in tibial plateau fractures was rather infrequent even in this large trauma center, but when performed, it revealed clinically significant information, thus benefitting patients in regard to treatment.

Ischemia-reperfusion injury in human liver transplantation : Mechanisms and effects on graft function

Liver transplantation is an established therapy for both acute and chronic liver failure. Despite excellent long-term outcome, graft dysfunction remains a problem affecting up to 15-30% of the recipients. The etiology of dysfunction is multifactorial, with ischemia-reperfusion injury regarded as one of the most important contributors. This thesis focuses on the inflammatory response during graft procurement and reperfusion in liver transplantation in adults. Activation of protein C was examined as a potential endogenous anti-inflammatory mechanism. The effects of inflammatory responses on graft function and outcome were investigated. Seventy adult patients undergoing liver transplantation in Helsinki University Central Hospital, and 50 multiorgan donors, were studied. Blood samples from the portal and the hepatic veins were drawn before graft procurement and at several time points during graft reperfusion to assess changes within the liver. Liver biopsies were taken before graft preservation and after reperfusion. Neutrophil and monocyte CD11b and L-selectin expression were analysed by flow cytometry. Plasma TNF-α, IL-6, IL-8, sICAM-1, and HMGB1 were determined by ELISA and Western-blotting. HMGB1 immunohistochemistry was performed on liver tissue specimens. Plasma protein C and activated protein C were determined by an enzyme-capture assay. Hepatic IL-8 release during graft procurement was associated with subsequent graft dysfunction, biliary in particular, in the recipient. Biliary marker levels increased only 5 7 days after transplantation. Thus, donor inflammatory response appears to influence recipient liver function with relatively long-lasting effects. Hepatic phagocyte activation and sequestration, with concomitant HMGB1 release, occurred during reperfusion. Neither phagocyte activation nor plasma cytokines correlated with postoperative graft function. Thus, activation of the inflammatory responses within the liver during reperfusion may be of minor clinical significance. However, HMGB1 was released from hepatocytes and were also correlated with postoperative transaminase levels. Accordingly, HMGB1 appears to be a marker of hepatocellular injury.

Heme oxygenase-1 in cardiovascular diseases

Myocardial infarction (MI) and heart failure are major causes of morbidity and mortality worldwide. Treatment of MI involves early restoration of blood flow to limit infarct size and preserve cardiac function. MI leads to left ventricular remodeling, which may eventually progress to heart failure, despite the established pharmacological treatment of the disease. To improve outcome of MI, new strategies for protecting the myocardium against ischemic injury and enhancing the recovery and repair of the infarcted heart are needed. Heme oxygenase-1 (HO-1) is a stress-responsive and cytoprotective enzyme catalyzing the degradation of heme into the biologically active reaction products biliverdin/bilirubin, carbon monoxide (CO) and free iron. HO-1 plays a key role in maintaining cellular homeostasis by its antiapoptotic, anti-inflammatory, antioxidative and proangiogenic properties. The present study aimed, first, at evaluating the role of HO-1 as a cardioprotective and prohealing enzyme in experimental rat models and at investigating the potential mechanisms mediating the beneficial effects of HO-1 in the heart. The second aim was to evaluate the role of HO-1 in 231 critically ill intensive care unit (ICU) patients by investigating the association of HO-1 polymorphisms and HO-1 plasma concentrations with illness severity, organ dysfunction and mortality throughout the study population and in the subgroup of cardiac patients. We observed in an experimental rat MI model, that HO-1 expression was induced in the infarcted rat hearts, especially in the infarct and infarct border areas. In addition, pre-emptive HO-1 induction and CO donor pretreatment promoted recovery and repair of the infarcted hearts by differential mechanisms. CO promoted vasculogenesis and formation of new cardiomyocytes by activating c-kit+ stem/progenitor cells via hypoxia-inducible factor 1 alpha, stromal cell-derived factor 1 alpha (SDF-1a) and vascular endothelial growth factor B, whereas HO-1 promoted angiogenesis possibly via SDF-1a. Furthermore, HO-1 protected the heart in the early phase of infarct healing by increasing survival and proliferation of cardiomyocytes. The antiapoptotic effect of HO-1 persisted in the late phases of infarct healing. HO-1 also modulated the production of extracellular matrix components and reduced perivascular fibrosis. Some of these beneficial effects of HO-1 were mediated by CO, e.g. the antiapoptotic effect. However, CO may also have adverse effects on the heart, since it increased the expression of extracellular matrix components. In isolated perfused rat hearts, HO-1 induction improved the recovery of postischemic cardiac function and abrogated reperfusion-induced ventricular fibrillation, possibly in part via connexin 43. We found that HO-1 plasma levels were increased in all critically ill patients, including cardiac patients, and were associated with the degree of organ dysfunction and disease severity. HO-1 plasma concentrations were also higher in ICU and hospital nonsurvivors than in survivors, and the maximum HO-1 concentration was an independent predictor of hospital mortality. Patients with the HO-1 -413T/GT(L)/+99C haplotype had lower HO-1 plasma concentrations and lower incidence of multiple organ dysfunction. However, HO-1 polymorphisms were not associated with ICU or hospital mortality. The present study shows that HO-1 is induced in response to stress in both experimental animal models and severely ill patients. HO-1 played an important role in the recovery and repair of infarcted rat hearts. HO-1 induction and CO donor pretreatment enhanced cardiac regeneration after MI, and HO-1 may protect against pathological left ventricular remodeling. Furthermore, HO-1 induction potentially may protect against I/R injury and cardiac dysfunction in isolated rat hearts. In critically ill ICU patients, HO-1 plasma levels correlate with the degree of organ dysfunction, disease severity, and mortality, suggesting that HO-1 may be useful as a marker of disease severity and in the assessment of outcome of critically ill patients.

Merkel cell carcinoma : Epidemiological study with special reference to polyomavirus and vascular factors in pathogenesis

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy that occurs predominantly on sun exposed skin areas. A new polyomavirus (MCPyV) was identified in MCC tumor tissues in 2008 suggesting that a viral infection might be an etiological factor. A typical MCC is a rapidly growing painless purple nodule. In its early stage it can be misjudged by its appearance as a cyst or abscess. Recurrences are common and approximately half of the patients will develop lymph node metastases and third of the patents will have distant metastases. It affects mostly elderly persons at an average age of 70 at the time of diagnosis. MCC was first described in 1972 and the first MCC patient in Finland was identified in 1983. MCC has been poorly recognized, but increased awareness and better diagnostic accuracy has increased the incidence since the early years. In this study, all cases with a notation of MCC during 1979 2008 were obtained from the Finnish Cancer Registry. Based on this data, the incidence is 0.11 for men and 0.12 for women. It is similar than that of other Nordic countries, but lower than in the USA. For clinical series, the files of patients diagnosed with MCC during 1983 2004 were reviewed, and the tissue samples were re-evaluated, if available (n=181). Third of the patients were men, and the most common site of the primary tumor was the head and neck (53%). The majority of the patients (86%) presented with a clinically node-negative (Stage I or II) disease, but the disease recurred in 38% of them. The treatment schemes were heterogeneous. No additional benefit from a wide margin (≥2 cm) was found compared to a margin of 0.1-1.9 cm, but intralesional excision was more often associated with local recurrence. None of the patients with Stage I-II disease who had received postoperative radiotherapy had local recurrence during the follow-up period. The 5-year relative survival ratio for Stage I disease was 68%, for Stage II 67%, for Stage III 16%, and for Stage IV 0%. The relative excess risk of death was significantly lower among women than among men. Some of these tissue samples were further analyzed for vascular invasion (n=126) by immunohistochemistry using vascular endothelial markers CD-31 and D2-40. Vascular invasion was seen in 93% of the samples and it was observed already in very small, <5mm tumors. The tissue samples were also analyzed for the presence of MCPyV by using a polymerase chain reaction (PCR) and quantitative PCR. MCPyV DNA was present in 80% of 114 samples studied. The patients with virus-positive tumors had better overall survival than patients with virus-negative tumors. Immunohistochemical analyses were performed for the expression of VEGFR-2 (n=21) and endostatin (n=19), but they had no prognostic value. Our results support the concept of treating MCC with margin-negative excision and radiotherapy to the tumor bed to reduce local recurrence. The finding of a high frequency of lymphovascular invasion reduces its value as a prognostic factor, but emphasizes the role of sentinel node biopsy even in very small primary MCC.

Excimer laser refractive surgery : corneal wound healing and clinical results

Although the first procedure in a seeing human eye using excimer laser was reported in 1988 (McDonald et al. 1989, O'Connor et al. 2006) just three studies (Kymionis et al. 2007, O'Connor et al. 2006, Rajan et al. 2004) with a follow-up over ten years had been published when this thesis was started. The present thesis aims to investigate 1) the long-term outcomes of excimer laser refractive surgery performed for myopia and/or astigmatism by photorefractive keratectomy (PRK) and laser-in situ- keratomileusis (LASIK), 2) the possible differences in postoperative outcomes and complications when moderate-to-high astigmatism is treated with PRK or LASIK, 3) the presence of irregular astigmatism that depend exclusively on the corneal epithelium, and 4) the role of corneal nerve recovery in corneal wound healing in PRK enhancement. Our results revealed that in long-term the number of eyes that achieved uncorrected visual acuity (UCVA)≤0.0 and ≤0.5 (logMAR) was higher after PRK than after LASIK. Postoperative stability was slightly better after PRK than after LASIK. In LASIK treated eyes the incidence of myopic regression was more pronounced when the intended correction was over >6.0 D and in patients aged <30 years.Yet the intended corrections in our study were higher for LASIK than for PRK eyes. No differences were found in percentages of eyes with best corrected visual acuity (BCVA) or loss of two or more lines of visual acuity between PRK and LASIK in the long-term. The postoperative long-term outcomes of PRK with two different delivery systems broad beam and scanning laser were compared and revealed no differences. Postoperative outcomes of moderate-to-high astigmatism yielded better results in terms of UCVA and less compromise or loss of two more lines of BCVA after LASIK that after PRK.Similar stability for both procedures was revealed. Vector analysis showed that LASIK outcomes tended to be more accurate than PRK outcomes, yet no statistically differences were found. Irregular astigmatism secondary to recurrent corneal erosion due to map-dot-fingerprint was successfully treated with phototherapeutic keratectomy (PTK). Preoperative videokeratographies (VK) showed irregular astigmatism. However, postoperatively, all eyes showed a regular pattern. No correlation was found between pre- and postoperative VK patterns. Postoperative outcomes of late PRK in eyes originally subjected to LASIK showed that all (7/7) eyes achieved UCVA ≤0.5 at last follow-up (range 3 — 11 months), and no eye lost lines of BCVA. Postoperatively all eyes developed and initial mild haze (0.5 — 1) into the first month. Yet, at last follow-up 5/7 eyes showed a haze of 0.5 and this was no longer evident in 2/7 eyes. Based on these results, we demonstrated that the long-term outcomes after PRK and LASIK were safe and efficient, with similar stability for both procedures. The PRK outcomes were similar when treated by broad-beam or scanning slit laser. LASIK was better than PRK to correct moderate-to-high astigmatism, yet both procedures showed a tendency of undercorrection. Irregular astigmatism was proven to be able to depend exclusively from the corneal epithelium. If this kind of astigmatism is present in the cornea and a customized PRK/LASIK correction is done based on wavefront measurements an irregular astigmatism may be produced rather than treated. Corneal sensory nerve recovery should have an important role in the modulation of the corneal wound healing and post-operative anterior stromal scarring. PRK enhancement may be an option in eyes with previous LASIK after a sufficient time interval that in at least 2 years.

Pain measurement and management in elderly patients : Clinical studies in long term hospital care and after cardiac surgery

The proportion of patients over 75 years of age, receiving all different types of healthcare, is constantly increasing. The elderly undergo surgery and anaesthetic procedures more often than middle-aged patients. Poor pain management in the elderly is still an issue. Although the elderly consumes the greatest proportion of prescribed medicines in Western Europe, most clinical pharmacological studies have been performed in healthy volunteers or middle-aged patients. The aim of this study was to investigate pain measurement and management in cognitively impaired patients in long term hospital care and in cognitively normal elderly patients after cardiac surgery. This thesis incorporated 366 patients, including 86 home-dwelling or hospitalized elderly with chronic pain and 280 patients undergoing cardiac surgery with acute pain. The mean age of patients was 77 (SD ± 8) years and approximately 8400 pain measurements were performed with four pain scales: Verbal Rating Scale (VRS), the Visual Analogue Scale (VAS), the Red Wedge Scale (RWS), and the Facial Pain Scale (FPS). Cognitive function, depression, functional ability in daily life, postoperative sedation and postoperative confusion were assessed with MMSE, GDS, Barthel Index, RASS, and CAM-ICU, respectively. The effects and plasma concentrations of fentanyl and oxycodone were measured in elderly (≥ 75 years) and middle-aged patients (≤ 60 years) and the opioid-sparing effect of pregabalin was studied after cardiac surgery. The VRS pain scores after movement correlated with the Barthel Index. The VRS was most successful in the groups of demented patients (MMSE 17-23, 11-16 and ≤ 10) and in elderly patients on the first day after cardiac surgery. The elderly had a higher plasma concentration of fentanyl at the end of surgery than younger patients. The plasma concentrations of oxycodone were comparable between the groups. Pain intensity on the VRS was lower and the sedation scores were higher in the elderly. Total oxycodone consumption during five postoperative days was reduced by 48% and the CAM-ICU scores were higher on the first postoperative day in the pregabalin group. The incidence of postoperative pain during movement was lower in the pregabalin group three months after surgery. This investigation demonstrates that chronic pain did not seem to impair daily activities in home-dwelling Finnish elderly. The VRS appeared to be applicable for elderly patients with clear cognitive dysfunction (MMSE ≤17) and it was the most feasible pain scale for the early postoperative period after cardiac surgery. After cardiac surgery, plasma concentrations of fentanyl in elderly were elevated, although oxycodone concentrations were at similar level compared to middle-aged patients. The elderly had less pain and were more sedated after doses of oxycodone. Therefore, particular attention must be given to individual dosing of the opioids in elderly surgical patients, who often need a smaller amount for adequate analgesia than middle-aged patients. The administration of pregabalin reduced postoperative oxycodone consumption after cardiac surgery. Pregabalin-treated patients had less confusion, and additionally to less postoperative pain on the first postoperative day and during movement at three months post-surgery. Pregabalin might be a new alternative as analgesic for acute postoperative and chronic pain management in the elderly. Its clinical role and safety remains to be verified in large-scale randomized and controlled studies. In the future, many clinical trials in the older category of patients will be needed to facilitate improvements in health care methods.