Assessment and management of pain in neonates treated with mild hypothermia following neonatal asphyxia

____________________________________________________________________________________________ 2 SWEDISH SUMMARY ________________________________________________________________________________ 3 CONTENTS _____________________________________________________________________________________________ 4 LIST OF ABBREVIATIONS __________________________________________________________________________ 5 INTRODUCTION ______________________________________________________________________________________ 6 AIM ______________________________________________________________________________________________________9 METHODS ______________________________________________________________________________________________ 9 LITERATURE SEARCH__________________________________________________________________________________ 9 RETROSPECTIVE COHORT STUDY____________________________________________________________________ 10 Population and settings ___________________________________________________________________________10 Inclusion and exclusion criteria___________________________________________________________________10 Periods of study and pain assessments____________________________________________________________10 Statistical analyses ________________________________________________________________________________12 RESULTS______________________________________________________________________________________________ 12 LITERATURE SEARCH________________________________________________________________________________ 12 SUMMARY OF THE LITERATURE _____________________________________________________________________ 12 The relationship between neonatal neurological impairment (such as asphyxia) and pain _____12 Mechanisms behind cold-induced pain ___________________________________________________________14 The experience of cold pain _______________________________________________________________________15 The effect of hypothermia on pharmacokinetics and pharmacodynamics________________________18 RETROSPECTIVE COHORT STUDY____________________________________________________________________ 20 DISCUSSION _________________________________________________________________________________________ 30 The relationship between neonatal neurological impairment (such as asphyxia) and pain _____30 Mechanisms behind cold pain_____________________________________________________________________32 The experience of cold pain _______________________________________________________________________32 Hypothermia and the neonatal pain expression __________________________________________________33 The effect of hypothermia on pharmacokinetics and pharmacodynamics________________________33 CONCLUSION________________________________________________________________________________________ 34 LIMITATIONS _______________________________________________________________________________________ 34 FUTURE DIRECTIONS _____________________________________________________________________________ 35 ACKNOWLEDGEMENT____________________________________________________________________________ 35 REFERENCES________________________________________________________________________________________ 36 APPENDIX ____________________________________________________________________________________________ 41