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AN OBSERVATIONAL STUDY IN SURGICAL PATIENTS WHO HAVE BEEN MECHANICALLY VENTILATED FOR MORE THAN 24 HOURS IN
SURGICAL ICU TO ESTIMATE THE INCIDENCE OF DELUSIONAL MEMORY AND DETERMINE THE CORRELATION BETWEEN DEVIATION IN RASS (RICHMOND AGITATION SEDATION SCALE)
SCORES AND THE OCCURRENCE OF DELUSIONAL MEMORY.
A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE
REQUIREMENT OF THE TAMILNADU DR.M.G.R MEDICAL UNIVERSITY, CHENNAI, FOR THE DEGREE OF M.D.ANAESTHESIOLOGY (BRANCH X) TO BE HELD IN APRIL 2014.
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CERTIFICATE
This is to certify that the dissertation entitled “An observational study in surgical patients who have been mechanically ventilated for more than 24 hours in surgical ICU to estimate the incidence of delusional memory and determine the correlation between deviation in RASS (Richmond Agitation Sedation Scale) scores and the occurrence of delusional memory.” Is the bonafide original work of Dr.Bharath.K in the partial fulfillment of the requirements for the
M.D.Anaesthesiology (Branch X) degree examination of the Tamilnadu Dr.M.G.R medical university, Chennai, to be held in April 2014.
HEAD OF THE DEPARTMENT GUIDE
Dr. MARY KORULA Dr. SUBRAMANI KANDASAMY Professor & Head Professor & Head
Department of Anaesthesia Surgical Intensive Care Unit &
Christian Medical College. Division of Critical Care.
Vellore - 632004 Christian Medical College.
Vellore-632004.
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Paper ID 377559285
Paper title RASS scores and delusional memories Assignment title Medical
Author Bharath k
E-mail bharath2kmc@gmail.com
Submission time 26-Nov-2013 01:28PM Total words 13102
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Introduction: More than four million patients in the United States of America and around 130,000 patients in the United Kingdom are admitted to the intensive care units annually1. Patients admitted to
intensive care units have severe life threatening illnesses and ICUs have the highest in hospital mortality rates. With improvements in the health care delivery systems and the field of intensive care itself, more and more patients are surviving their stay in ICU. As these survivors of critical illness come for their follow up or visit the hospital for other illness, the long term effects of their ICU stay become apparent. In the past few years researchers have been focusing on these long term...
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TABLE OF CONTENTS
Page No
INTRODUCTION 13
LITERATURE REVIEW - HISTORY AND EVOLUTION 15
- ROLE OF SEDATION AND ANALGESIA 20
- PHARMACOLOGY OF DRUGS 27
- SEDATION SCORING SYSTEMS 41
- MEMORY FORMATION 48
- POST TRAUMATIC STRESS DISORDER 57
MATERIALS AND METHODS 64
RESULTS 70
LIMITATIONS OF THE STUDY 88
CONCLUSION 89
BIBLIOGRAPHY 90
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APPENDICES
1. DSM 5 CRITERIA 94
2. ICU MEMORY TOOL 98
3. MODIFIED ICU MEMORY TOOL 100
4. PROFORMA 102
5. PATIENT INFORMATION SHEET 108
6. CONSENT FORM 112
7. MASTER SHEET 115
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Acknowledgement
Working on thesis has been a great experience for me.
It gives me immense pleasure to express my heartfelt and profound sense of gratitude to my respected teacher and guide, Dr. Subramani Kandasamy for his valuable suggestions, meticulous guidance, support and encouragement during this study.
I am grateful for the support I received from the Heads of the various surgical departments from whom I have recruited patients.
I thank Dr. Mary Korula her support in conducting this study.
I thank the entire nursing team of the Surgical Intensive Care Unit for their cooperation and valuable support.
I would also like to thank the department of Clinical Epidemiology and Department of Biostatistics who helped me with the design of this study and analysis of data.
I am grateful to my wife and parents for their moral support and encouragement throughout my carrier.
I am grateful to god for his grace and wisdom.
Last, but not the least, I thank all my patients for their cooperation, in this study.
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Introduction:
More than four million patients in the United States of America and around 130,000 patients in the United Kingdom are admitted to the intensive care units annually1. Patients admitted to intensive care units have severe life threatening illnesses and ICU’s have the highest in hospital mortality rates. With improvements in the health care delivery systems and the field of intensive care itself, more and more patients are surviving their stay in ICU. As these survivors of critical illness come for follow up or visit the hospital for other illness, the long-term effects of their ICU stay become apparent. In the past few years’ researchers have been focusing on these long term outcomes.
One of the long-term problems of survivors of critical illness is ‘Post traumatic stress disorder’. During their stay in ICU the patients are experiencing not just life
threatening illness but are subject to ICU therapies that are extremely stressful. This is combined with their inability to communicate and reduced autonomy. When the
patients are discharged from the ICU, they leave with memories of these stressful events, which in the future result in the development of post-traumatic stress disorder.
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The chain of events in the development of post traumatic stress disorder.
patients with life threatening critical
illness subject to ICU therapies.
memories of ICU stay.
post traumatic stress disorder.
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History and evolution of intensive care medicine.
Critical care is a young discipline which has rapidly grown into a full specialty of its own. Every day the number of patients with life threatening complex disease is ever increasing and as a result the ratio of intensive care unit beds to general beds has been steadily increasing. The evolution of technology and scientific advance in clinical medicine has been most apparent in the field of critical care.
Origins of intensive care:
The origin of intensive care can be traced to the Crimean war of the 1850’s where the battle wounded British soldiers were cared for by over worked medical staff, with neglected hygiene, sparse medical supply and mass infection were common. Florence Nightingale advocated that most seriously ill patients should be placed proximal to the nursing station. She recognized the need for monitoring the sickest soldiers more regularly by nurses. Thus she is credited with creating an early focus on the
importance of a separate geographical area for severely ill patients. This event is most cited as the beginning of critical care.23,4
During the Second World War hemorrhagic shock was a major problem.
Specialized shock units were setup to provide prompt and efficient resuscitation to a large number of bleeding soldiers.4
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Evolution of respiratory care:
Although the intensive care units are a modern concept, the history of organ
support dates back to many thousand years. Hippocrates had initiated a form of organ support by cannulating the airway to facilitate ‘air to be drawn into the lungs’.5
In 1950 the city Copenhagen in Denmark experienced severe polio epidemic. The spectrum of severity ranged from simple illness to bulbar poliomyelitis and profound respiratory paralysis. The option available at that time was the ‘Iron lung’ invented by Philip Denker, which comprised of a box encompassing the patient’s body excluding the head6. It was bulky and an expensive device and not available in sufficient
numbers to cater to the bulk of the polio epidemic. Many patients were dying of respiratory failure.
Dr. Bjorn Ibsen, a Danish anesthesiologist proposed than the patients could be taken care by performing a tracheostomy and ventilating the lungs manually with oxygen/nitrogen mixture with positive pressure. The patients were manually ventilated by medical students3. These were the events leading to out-of-operating room airway intubation and mechanical ventilation. He recognized the importance of carbon dioxide clearance and suggested that carbon dioxide absorbers be incorporated into the breathing circuits. At a time more than seventy patients were being mechanically
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ventilated this way and reduction of mortality from 80% to 25% was achieved. Dr.
Ibsen opened the first intensive care unit in the United Kingdom in 19537.
Subsequently the development of piston ventilators, application of electronics in the sensing of patients respiratory dynamics and programming of the modes of delivery of mechanical ventilation has lead to better respiratory organ support.
Recognition of patient comfort factor:
By its nature, critical care units are not pleasant places to be in. There is a constant environment of activity, bright lights, noise adding to the ever present perception of threat that the patients feel towards medical interventions. Pain, loneliness and fear are constant companions and it is a challenge to the treating physicians to address these issues.
Martin Holmdahl, one of the fathers of modern critical care, developed a system where every patient who is mechanically ventilated had one person to sit at the bedside. Medical students, technicians, housewives were hired for a modest fee to accompany the patients8. Years later Peter Safar wrote that every patient maintained on mechanical ventilation should be accompanied by a person, who need not be medically educated, but a well trained individual9.
Sedation of the patients in critical care units has become an important tool in
handling the problems faced by the patients and improving patient comfort. It has now
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become a standard of care to sedate all patients who are being mechanically ventilated for various reasons such as endotrachial tube tolerance, analgesia and patient comfort.
Concept of patient nurse ratio:
With the patients in ICUs having a multitude of different infections and the presence of opportunistic infections, prevention of cross infection from patient to patient becomes important. This has lead to the discussion on how many patients do individual nurses cater to. Studies have shown that a reduction of patient to nurse ratio leads to reduction in the hospital acquired infection and post operative
complications10,11.
Evidence based medicine in intensive care:
With the development in science and technology interventions in intensive care had become excessive in the early years. Subsequently research and an evidence based approach has identified interventions that are not beneficial or harmful and help
physicians use interventions only on as and when required basis. The few changes that evidence based medicine has made to the intensive care field include low tidal volume ventilation in Acute lung injury/Acute respiratory distress syndrome, increased use of non invasive ventilation, less use of sedation, emphasis on nutrition and less generous calorie intake, less invasive monitoring systems, less use of inotropes to increase
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oxygen delivery to supra normal levels, minimal blood transfusions and restrictive antibiotic therapy12.
Progress with therapeutics:
There have been very few major developments in intensive care in terms of specific treatments and cures in the past few years. Although our basic scientific knowledge and understanding of the pathophysiology of syndromes like Sepsis and Acute Respiratory Distress Syndrome have improved, the translation of this
knowledge into specific therapeutics have met with little success. This could be due to the variable and complex nature of the disease process, the heterogeneous nature of the patients affected and in adequate preclinical models available currently13. The large number of multicentre randomized control trials might indicate maturity of the field but majority of them have failed to demonstrate improved outcomes with the intervention studied14.
Challenges for the future:
The patients admitted to intensive care are getting older and sicker, as a result more strain is placed on the resources that are sparse and prohibitive to some population in terms of cost. The challenge in the future is not only provide effective, efficient and evidence based care but one that is comfortable and humane to the patients.
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Role of sedation and analgesia in the intensive care unit:
Sedation and analgesia are very important aspects of patient care in intensive care units. Generally sedation is used in intensive care patients to make them comfortable in their environment or at least be tolerant to the perceived hostility of the ICU. There are many sedative and analgesic drugs that are available to the intensivist to choose from, but the research evidence that helps the physician to choose one drug over the other is largely lacking. The vast majority of studies that have been done on sedation are largely before/after studies and very few randomized control studies have been done, as a result the choice of the drug is based on the pharmacological properties of the drug and not evidenced based.
Need for sedation in the intensive care:
Most patients in the intensive care unit are aware of the life threatening nature of their illness. This along with inability to communicate and lack of control are major cause of anxiety in mechanically ventilated patients15. The factors that contribute to the stress of the patient in the intensive care unit are noise from monitors, telephones, physician/nurse conversation, physicians discussing the patient condition over the bedside, lack of day and night awareness, feeling of loneliness, boredom, pain originating from the surgery undergone or the various invasive monitoring
undertaken, back ache from lying down in an uncomfortable position, lack of seep,
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medication side effects, nursing interventions like suctioning and turning and if patients are not segregated adequately then they may be a witness to other patients suffering too.
This environment is perceived by the patient as stress full. This results in a physiological stress response that is characterized by sympathetic nervous system activation and cortisol release, causing increased work of the cardiovascular and the respiratory systems and suppression of immunity.
Delirium and altered sensorium are common complications encountered in the intensive care patients. They are often unrecognized and are a significant cause for morbidity, prolongation of stay in ICU and adding cost to the overall healthcare16. The patients may pull on their invasive access lines or self extubate which may result in bleeding, trauma to the airway and if prompt intervention is not made, even death.
Agitated and combative patients can be a threat to the health care workers too.
Pain experienced by the patients in the intensive care is a major cause for anxiety and could be one of the unrecognized causes for delirium and agitation in patients.
Unrelieved pain can produce the stress response17 which can result in harmful multi system effects. Good acute pain management is an essential part of holistic patient care.
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Sedation is an important tool in treating anxiety and pain in the intensive care unit.
It helps the patient to accept the environment and in some cases helps the physician in making the patients less aware to the stress inducing events in the intensive care.
Assessment of the need for sedation, initiation and maintenance, continuous
monitoring of its adequacy and weaning are the important aspects of management of sedation in intensive care.
Ideal sedative agent:
An ideal sedative should not only be cheap/cost effective its use should decrease the overall cost of health care in terms of lower number of ventilator and ICU days, should not have any active metabolites that accumulate in the body, should have both analgesic and sedative effects, minimal cardiovascular side effects, controllable respiratory effects, rapid onset and offset of action, should not accumulate in renal or hepatic failure and should have minimal interaction with other drugs.
Route of administration:
Oral route of administration is generally not preferred, as severely ill patients have delayed gastric emptying, stress ulceration of the gastric mucosa, unpredictable first pass metabolism. Patients with continuous gastric drainage by nasogastric tube and on high dose of inotropes are not suitable for use of oral drugs. Therefore in most patients parenteral route of administration is preferred for sedation18.
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Initiation and maintenance:
Sedative drugs can be administered either by intermittent boluses or by continuous infusion. The problem with intermittent boluses is that the patient’s consciousness levels can fluctuate between unresponsive to agitated as soon as the drug is
administered just before the next dose is due. Therefore continuous infusions are the preferred mode of administration.
Any infusion that has been started takes four half lives to reach steady state
concentration, therefore any sedative drug to be effective takes significant amount of time and any dose adjustments to the infusion also takes long time to be effective.
The right way of administering these drugs is by giving a loading dose titrated to effect followed by a continuous infusion. For dose adjustments, a bolus dose followed by an increase in infusion rate is ideal.
Hypnosedation Vs analgosedation:
Pain is the primary cause for all distress in intensive care patients1920. Joint Commission on Accreditation of Healthcare Organization has made it mandatory to monitor pain in all patients admitted in intensive care units.
The right way to sedate a patient would be to assess the pain level of the patient, initiate analgesia and then add on a hypnotic agent to allay the anxiety if required.
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Hypnosedation is a hypnotic based sedation protocol and analgosedation is an analgesia based sedation protocol. Studies have shown that analgosedation is as effective as hypnosedation and the added advantage is that the dose of the hypnotic agent is reduced2118.
Complication of sedation:
Prolonged administration of sedative drugs can cause accumulation of the sedative drugs and its metabolites leading to problems with weaning and longer ICU stay, over dosing can lead to circulatory problems resulting in increased use of inotropes,
detrimental effects on the lungs causing ventilation/perfusion mismatch and increasing ventilatory support, suppression of cough reflex and reducing clearance of pulmonary secretions, their inability to produce REM sleep may lead to psychosis, reduced
intestinal motility causing constipation and impairing enteral feeding and the grave risk of withdrawal symptoms during stoppage and risk of dependence22.
Non pharmacological methods of aiding sleep/sedation:
Employing non pharmacological methods to increase the comfort levels of the patient will result in decreased requirement of the overall dose of sedatives.
Constant communication to the patient regarding the medical condition and the therapies by the doctors, nurses and relatives, introduction of quiet hours in ICU, not discussing grave prognosis near the patient, allowing liberal visiting by the relatives
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and measures to improve sleep by mimicking physiological conditions(dimming the lighting during the night) and music therapy are some of the non pharmacological measures employed to increase the comfort level of the patent and reduce the dose of sedative drugs used.
Concept of sedation holiday:
Earlier, sedative drugs were used as intermittent boluses and this did not provide a steady state blood concentration and the patient’s sensorium was fluctuating,
moreover monitoring the patient’s condition and timely repeated administration of sedative drugs often with consultation with doctors placed undue stress on the nursing services. Hence most ICUs administer sedative drugs by continuous infusion.
Continuous infusion of sedative drugs carries its own problems. It is an
independent predictor of longer duration of mechanical ventilation, ICU stay and the overall hospital stay23. Assessment of neurological status in patients who are deeply sedated is difficult and this causes the treating physicians to over order radiological imaging like Magnetic Resonance Imaging and Computed Tomography when patients do not wake up immediately after stopping the infusion of sedative drugs.
As a solution to this problem, the concept of ‘daily interruption of sedation’ was introduced by Kress and colleagues in 199624. This process is stoppage of sedation every day at a predetermined time, waiting for the patient to be fully awake,
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completion of the necessary neurological examination and restarting the sedative drugs.
Daily interruption of sedation is contraindicated in patients with raised intra cranial pressure, evidence of ischemia to the myocardium in the past 24 hours, patients who are receiving neuro-muscular blockers, ongoing agitation with need for escalating sedative requirement and when sedatives are being given to treat ongoing seizures or alcohol withdrawal.
Daily interruption of sedation is associated with early weaning from mechanical ventilation, shorter length of ICU stay and lower incidence of symptoms of post traumatic stress disorder on long term follow up25. This practice also decreases the total dose of benzodiazepines used during the patients ICU stay26.
The criticism against daily interruption of sedation is that it might increase the chances of the patient self extubating, may increase anxiety and intolerance to the ICU environment. Studies done so far have only shown a favorable benefit versus risk and researchers continue to study this concept to gather evidence on this practice.
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Pharmacology of common sedative drugs used in ICU:
Morphine:27
Opioids are alkaloids of the juice of the poppy seeds. Twenty different alkaloids are sourced from the juice and they can be divided into two distinct chemical classes the phenantherenes and benzylisoquinolines. Morphine is the principal phenantherene alkaloid present in opium.
Opioids bind to steriospecific opioid receptors at the presynaptic and post synaptic sites in the central nervous system. They act as agonists causing analgesia, euphoria, sedation and decreased ability to concentrate.
Opioid receptors are classified as mu, delta and kappa. The physiological agonists to these receptors are the endogenous opioids, which are endorphins, enkephalins and dynorphins. Exogenous opioid drugs when administered bind to the opioid receptors and mimic the action of endogenous opioids. The binding causes pre synaptic hyper polarization by increased potassium conductance and inhibition of calcium channel leading decreased release of neuro transmitters acetylcholine, dopamine, nor-
epinephrine and substance P.
The penetration of morphine into CNS is poor and morphine has poor lipid solubility, high degree of ionization and protein binding and is rapidly conjugated with glucuronic acid in both hepatic and extra hepatic sites. The principal metabolites
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are morphine-3-glucuronide and 6-glucuronide. The former is metabolically inactive but the 6-glucuronide can produce analgesia and depression of ventilation.
The physiological effects of morphine include depression of ventilation, direct myocardial depression in large doses, cough suppression, sedation, biliary spasm, constipation, delayed gastric emptying, nausea and vomiting.
Though morphine can be administered orally, intra muscularly and subcutaneously it is commonly administered as continuous IV infusion in ICUs at a dose range of 0.02-0.1mg/kg/hour for analgesia and sedation.
Fentanyl:28
Fentanyl is a synthetic opioid agonist derived from phenypiperidine and
structurally similar to meperidine. Along with midazolam it is the most commonly used sedative agent in the intensive care unit.
Fentanyl’s high lipid solubility aids its passage across blood brain barrier and accounts for a fast onset of action. After the first dose fentanyl is redistributed to inactive tissue sites such as fat and skeletal muscles. The lung has a very high first pass uptake (75%) for fentanly. Fentanyl therefore has a short duration of action. But prolonged infusion or repeated bolus administration saturates these sites and even when the drug is terminated the effects may persist and wakeup times prolonged as the tissues continue to add the drug to the blood stream.
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Fentanyl is extensively metabolized by N-demethylation to its principal metabolite Norfentanyl. Less than 10% is excreted unchanged in the urine. As fentanyl is a
substrate for CYP3A it is susceptible for drug interaction that modifies this enzyme activity.
The relative cardiovascular stability of fentanyl is due to its lack of direct
depressant effect on the myocardium. The carotid sinus baroreceptor reflex control of heart rate is markedly depressed and therefore a combination with other drugs can produce hypotension. Persistent or recurrent respiratory depression is a problem, as the drug accumulated in the non active sites is released into the blood stream.
Infusion doses of 0.3-1microgram /Kg/hour are used in ICU for analgesia and sedation. A transdermal patch delivering 25-100 micrograms /hour is available which reaches a peak plasma concentration at 18 hours and providing a stable blood level.
Sufentanil29:
Sufentanil is a thienyl analogue of fentanyl. As a result of its greater affinity towards opioid receptors sufentanil is ten times more potent than fentanyl.
High lipid solubility of sufentanil helps it to cross the blood brain barrier rapidly and produces quick CNS effects. Termination of action is by redistribution to inactive tissue sites and it undergoes significant first pass uptake in the lungs (60%). Sufentanil is extensively bound to alpha1-acid glycoprotein, conditions that increase or decrease
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this protein (surgery, neonates and infants) could alter the concentration of the pharmacologically active unbound sufentanil leading to unpredictable physiological response.
Sufentanil is rapidly metabolized by N-dealkylation and O-demethylation. 1% of the drug is excreted unchanged in the urine. The hemodynamic and respiratory effects are similar to that of fentanyl.
Alfentanil30:
Alfentanil is a less potent and shorter acting analogue of fentanyl. The unique advantage of alfentanil over sufentanil and fentanyl is the more rapid onset of action.
Although alfentanil is less lipid soluble and more protein bound in comparison to sufentanil and alfentanil, it has rapid effect site equilibrium time of 1.4 minutes as compared to fentanyl (6.8min) and sufentanil (6.2min). This is primarily due to the low pKa value of alfentanil. 90% of the drug remains in the non ionized form in the blood and therefore the penetration into the blood brain barrier is much faster.
Alfentanil is metabolized in the liver by the enzyme CYP3A and significant inter individual variability exists in alfentanil metabolism. This is a confounding factor in development of reliable infusion regimens to attain steady state concentration of the drug. Although alfentanil has a shorter elimination half life in comparison to
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sufentanyl the context sensitive half life is much greater due to its smaller volume of distribution.
Alfentanil is primarily used for providing analgesia when the noxious stimulus is acute but transient, for example endotrachial intubation and performance of
retrobulbar block.
Alfentanil can be used as bolus of 10-30microgram/Kg or as an infusion of 10- 100microgram/Kg/hour.
Remifentanil31:
Remifentanil is a synthetic opioid with an effect site equilibration time similar to alfentanil and analgesic efficacy similar to fentanil. Although chemically related to the fentanyl family the structure of remifentanil is unique because it has an ester linkage.
The ester linkage makes remifentanil susceptible to hydrolysis by nonspecific tissue and plasma esterases. Due to its unique metabolism it has very short duration of
action, precise and rapidly titratable effects, no cumulative effects and rapid recovery after stoppage of infusion. The only opioid whose context sensitive half life is
independent of the duration of administration is remifentanil. In addition to this remifentanil has a small volume of distribution and low inter individual variability, these properties combined make remifentanil an ideal drug in clinical settings requiring predictable elimination of drug effect.
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Remifentanil can be used as an infusion of 0.05-0.1 microgram/Kg/min as sedation.
It is commonly used along with midazolam or propofol. Midazolam produces a dose dependant potentiation of the respiratory depression of remifentanil.
Termination of the infusion of remifentanil can produce rebound pain and delayed hyperalgesia. Large dose of remifentanil use is associated with acute opioid tolerance.
As like all fentanyl analogues remifentanil induces seizure like activity.
Thiopental sodium:32
Thiopental sodium is a rapidly acting, short duration, barbiturate intravenous anaesthetic. Commonly used for induction of anaesthesia. It reaches the brain in one arm brain circulation time and the termination of action is by rapid redistribution.
It is a highly lipid soluble drug readily crossing the blood brain barrier. Due to its high fat:water partition coefficient it is sequestered in fatty tissues. The redistributed drug is metabolized in the liver to pentobarbital.
The barbiturate has anaesthetic, sedative, anxiolytic and hypnotic effects but lacks analgesic property. It is contraindicated in patients who are prone for acute
intermittent porphyria as thiopental can precipitate an episode.
Thiopental is not the first choice sedative agent in ICU as it tends to accumulate in fatty tissues and significantly prolong recovery times. It is used as an infusion in
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specific situations like intractable seizures and during the first 48 hours after traumatic brain injury. The infusion dose of Thiopental is 0.5-4mg/kg/hour.
Midazolam:33
Midazolam is a short acting drug belonging to the benzodiazepine class of drugs.
Midazolam has a unique chemical property, the immidazole ring in the molecule causes the drug to be water soluble in vitro, but in vivo the ring opens up and the drug becomes lipid soluble, thereby facilitating entry across blood brain barrier.
Mechanism of action is by acting as an indirect agonist to GABAA receptor. It facilitates the action of GABA on this receptor and causes the physiological effects of sedation, hypnosis, anxiolysis, anterograde amnesia, muscle relaxation and anti
convulsant effects.
Due to the property of anterograde amnesia, midazolam is used as a sedative premedication preoperatively. In intensive care continuous infusion of midazolam is used to sedate mechanically ventilated patients. Other uses of midazolam are
procedural sedation for endoscopy, treatment of insomnia, treatment of Schizophrenia with severe agitation and induction of anesthesia.
The infusion dose of midazolam for sedation is 0.02-0.1mg/kg/hour. A specific antagonist, Flumazenil is available to treat midazolam overdose.
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Lorazepam:34
Lorazepam is a sedative drug belonging to the benzodiazepine group. The mechanism of action and clinical effects are similar to that of midazolam.
Though lorazepam has a shorter elimination half life as compared to midazolam, the clinical duration of action is significantly longer because of its higher receptor affinity to GABAA.
Lorazepam has poor lipid solubility, it is conjugated at its 3-hydroxyl group with glucuronide to form inactive metabolite which is excreted in the urine. Very little drug is excreted unchanged in the urine and it does not show accumulation of active metabolites even after administration for six months.
Its predominant use in anesthetic practice is to use it as a sedative
premedication. In intensive care midazolam and Propofol are preferred over lorazepam as they exhibit faster recovery time.
Infusion dose of Lorazepam is 0.01-0.1mg/kg/hour, prolonged infusion of large doses have been found to produce hyper-osmolar states with lactic acidosis and renal tubular necrosis attributable to poly ethylene glycol and propylene glycol as solvents.
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Propofol:35
Propofol, chemically known as 2,6-diisopropylphenol is un related to other IV induction agents. As Propofol is insoluble in water it was first introduced as an
emulsion with ‘Cemafor EL’ but due to the anaphylactiod reaction to this preparation it was withdrawn from the market. Now it has been reformulated as a macroemultion containing glycerol, soya bean oil and egg yolk lecithin.
Mechanism of action is by direct activation of GABAA receptors and inhibitory action at the NMDA sub group of glutamate receptors has also been reported. It is highly protein bound and lipid soluble drug which has rapid penetration into the CNS.
It undergoes first pass uptake in the lungs and the heart before it enters the arterial circulation.
The termination of action of propofol is by rapid redistribution of the drug into fatty tissues. It is metabolized in the liver by the cytochrome P450 group of enzymes into inactive metabolites that are excreted in the urine. Though the elimination half life is prolonged after a long duration of infusion the context sensitive half life of clinical recovery is not affected.
Physiologically propofol produces depression of the cardiovascular system by direct myocardial depression, decreased stroke volume, decreased systemic vascular resistance and deceased cardiac output. It causes decrease in the cerebral metabolic
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rate, cerebral oxygen requirement, decreases the cerebral blood flow and decreases the intra cranial tension. It causes the depression of the respiratory centre, bradypnoea and depresses the laryngeal reflexes. In addition to this it is said to have anti emetic and anti oxidant properties.
It is primarily used as an induction agent in anesthesia, agent for conscious
sedation in intensive care, sedation of mechanically ventilated patients and procedural sedation for endoscopies. The dose of propofol for induction of anesthesia is 2-
2.5mg/kg and sedation dose is 25-75micrograms/kg/minute. Continuous infusion of large doses of propofol in children is known to cause severe metabolic acidosis, rhabdomyolysis in what is known as ‘propofol infusion syndrome’.
Etomidate:36
Etomidate is a carboxylated immidazole containing compound, which is water soluble at acidic pH and lipid soluble in physiological pH. The earlier preparations contained 35% of propylene glycol which caused severe pain on IV injection which has now been changed to fat emulsion.
The commercial preparations of Etomidate contain only the ‘R’ isomer which has five times more activity than the ‘L’ isomer. Etomidate binds to specific site on the GABAA receptor and facilitates the action of the neurotransmitter GABA, it does not modulate other ligand gated channels.
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The volume of distribution is large and it is 76% bound to serum albumin, in disease states which cause serum albumin to drop the concentration of free drug can drastically increase. The peak onset of action is within one minute and the termination of its action is due to redistribution.
The unique property of Etomidate as compared to other induction agents is its cardio stability. After administration of 0.3mg/kg of the drug there is little change in heart rate, stroke volume and cardiac output. This property of Etomidate makes it an ideal induction agent for patients with poor left ventricular function.
Etomidate causes adreno-cortical suppression. It causes dose dependent inhibition of the conversion of cholesterol to cortisol by inhibiting the enzyme 11-beta-
hydroxylase. Even a single dose of Etomidate can produce this effect that lasts upto four to eight hours. This effect may be undesirable in patients who are experiencing hemorrhage and Sepsis, these patients need the adreno-cortical response to be intact.
Therefore continuous infusion of Etomidate in intensive care for sedation is not recommended.
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Ketamine:37
Ketamine is a phencyclidine derivative that produces ‘dissociative anesthesia’ by dissociating the thalamo-cortical and the limbic system. After administering ketamine patients appear to be awake but they are non communicative, eyes remain open with slow nystagmus, they are amnestic and may show limb movements unrelated to surgical stimulation. The main advantage of ketamine over other IV induction agents is that sub anesthetic doses intense analgesia, but the possibility of patients
experiencing emergence delirium limits its clinical use.
Ketamine has two isomers , S and R. The S isomer produces more intense
analgesia, is metabolized faster, lesser salivation and lower incidence of emergence delirium. Ketamine is a non competitive antagonist at the N-methyl-D-aspartate receptor, it also has action on other sites like opioid receptors, monoaminergic
receptors, voltage sensitive sodium and L-type calcium channels but it has only weak action on GABAA receptors.
Ketamine has rapid onset of action due to its high lipid solubility and a rapid offset of action due to quick redistribution. It is metabolized by hepatic microsomal enzymes and one metabolite in particular, norketamine, has one fifth the potency of ketamine.
This metabolite tends to accumulate after prolonged infusion. The microsomal
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enzymes are subject to induction and for this reason patients receiving ketamine for prolonged period of time can develop tolerance to its analgesic action.
Ketamine is primarily used as an analgesic. It can be used as an induction agent in shock as it causes stimulation of the cardio vascular system and maintains cardiac output unlike other induction agents. It also has bronchodilatory action and can be used in sub-anesthetic doses to treat bronchospasm in the operating room or the ICU.
Dexmedetomidine:38
Dexmedetomidine is an alpha2-adrenergic receptor agonist. It is a unique sedative drug that does not cause any respiratory depression. Though it has a similar
mechanism of action as clonidine, dexmedetomidine has a much more selective action on the alpha2A subtype of adrenergic receptor.
By binding to these receptors in the brain and spinal cord, Dexmedetomidine inhibits neuronal firing and causes sedation, analgesia, hypotension and bradycardia.
Other physiological effect of this drug include, decreased salivation, decreased gut secretion and motility, decreased rennin release, increased GFR and decreased insulin release from the pancreas.
Dexmedetomidine is 96% protein bound and metabolized in the liver by
microsomal enzymes. Dose adjustment may be required in patients with liver failure.
Very little of the drug is secreted unchanged in the urine.
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The uses of Dexmedetomidine in anesthesia include, as premedication for both general and regional anesthesia, blunting the sympathetic response to laryngoscopy, intubation and surgical stimulation, it potentiates the action of all anesthetic drugs and reduces intraoperative and post operative opioid requirement. In the intensive care unit it is used to sedate patients on mechanical ventilation, both invasive and non invasive as it causes negligible respiratory depression. Dose of Dexmedetomidine is a bolus of 1-2microgram/kg followed by an infusion of 0.3-0.7microgram/kg/hour.
The safety of this drug is not established in pregnancy, therefore best avoided in pregnant ladies. The side effects of this drug are initial hypertension and bradycardia followed by hypotension, nausea and various atrio-ventricular blocks. These side effects are common after a large bolus dose and they can be minimized by reducing the initial bolus dose.
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Sedation scoring systems in ICU:
Almost all patients in ICU receive some form of sedation. Frequently patients are under or over sedated, this leads to morbidity, mortality and heavy economic
consequences. To prevent under or over sedation, we need to monitor sedation in the same intensity as we monitor the patient’s hemodynamics, oxygenation or
neurological function.
Various scoring systems are available to monitor the depth of sedation. The three most validated tools for sedation in adults include The Ramsay sedation scale39, The Richmond agitation sedation scale40 and the Motor activity assessment scale41. The Ramsay Sedation Scale(RSS):
The Ramsay sedation scale was designed primarily as a tool to assess arousability of patients on sedative drugs. This scale is very intuitive to use therefore the most common sedation scoring system used not only in ICU but wherever sedative drugs given.
The RSS scores sedation at six levels.
1. Patient is agitated and anxious or restless.
2. Patient is well oriented, co-operative and calm.
3. Patient responds only when commanded.
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4. Patient exhibits brisk response to loud auditory stimulus or light glabellar tap.
5. Patient exhibits sluggish response to loud auditory stimulus or light glabellar tap.
6. Patient exhibits no response.
The limitation of RSS is that it depends on the ability of the patient to respond
therefore patients on neuro muscular blockers cannot be assed with this scale. It does not tell us how severe is the agitation or how deeply the patient is sedated when the score is 6. In such situations EEG based monitoring systems are more useful.
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Using the RSS.
Yes no
Is the patient awake?
Anxious patient, score 1
Calm patient, score 2
Voice command.
Quick response, Score 3.
No response.
Louder auditory stimulus/glabellar tap.
Brisk response
Score 4. Slow response
Score 5.
No response Score 6.
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Richmond AgitationSedation Scale:
Richmond agitation sedation scale was developed as a collaborative effort between medical and paramedical staff to counter the limitations posed by various other
sedation scoring systems. RASS has a 10 point scale which has one value ‘0’ to indicate a calm and conscious state, describes an agitated or anxious state over four levels and describes sedation drowsiness and sleep over five levels.
RASS is administered in three sequential steps: observation of the patient, response of the patient to verbal stimulation and response to physical stimulation. RASS has been tested in patients from medical, surgical, cardiac surgical, coronary and
neurosurgical intensive care units and has been proven a valid tool with good inter- rater reliability42.
The scoring system is described below.
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Score. Term. Description.
+4 Combative. Overly violent combative and
immediate danger to staff.
+3 Very agitated. Pulls at tubes and catheters,
aggressive.
+2 Agitated. Frequent non purposeful
movements, fights ventilator.
+1 Restless. Movements are not aggressive or
vigorous but anxious.
0 Alert and calm.
-1 Drowsy. Not fully alert but has sustained
eye contact to voice(>10sec).
-2 Light sedation. Briefly awakens with eye contact
(<10sec).
-3 Moderate sedation. Movement or eye opening to voice
without eye contact.
-4 Deep sedation. No response to voice but eye
opening to physical stimulation.
-5 Unarousable. No response to stimulation.
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Motor activity assessment scale:
This is a sedation scale developed by an intensivist specifically for use in ICU. It categorizes mechanically ventilated patients based on responsiveness to stimulus. It has been validated by health care providers in surgical intensive care units41.
0 Unresponsive Does not move to noxious stimulus.
1 Responds only to noxious stimulus. Opens eyes OR raises eyebrows OR turns head towards stimulus OR moves limbs with noxious Stimulus.
2 Responds to touch or name. Opens eyes
OR raises eyebrows
OR turns head towards stimulus OR moves limbs when touched or name is loudly spoken.
3 Calm and co-operative. No external stimulus is required to elicit movement
AND patient is purposeful and follows commands.
4 Restless and co-operative. No external stimulus is required to elicit movement
AND patient is picking at sheets or tubes
OR uncovering self
AND follows commands.
5 Agitated. No external stimulus is required to
elicit movement
AND patient attempting to sit up OR moves limbs out of bed
AND does not consistently follow commands.
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6 Dangerously agitated. No external stimulus is required to elicit movement
AND patient is pulling at tubes or catheters
OR thrashing side to side or striking at staff
OR trying to climb out of bed AND does not calm down when asked.
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Physiology of memory formation:
Memory is a faculty by which the mind stores and remembers information.
The process of memory formation:
The process of memory involves encoding, storage and retrieval. Encoding
involves receiving an external stimulus, changing it, combining it and modifying it by virtue of past experiences and getting it ready for deposition in the memory inventory of the brain. Storage is the second process by which a permanent record is made of the information collected. The third process retrieval or recall is the return of the stored information to the consciousness. The effort taken for the third process depends on the type of information stored and the number of times the external stimulus was applied or perceived.
Brain structures involved in memory formation:
The brain structures involved in memory formation can be classified as the cortical and the sub-cortical structures. The cortical structures involved in memory are the Frontal lobe and the temporal lobe. The sub-cortical structures involved in memory are the Hippocampus, the Amygdala, the Cerebellum and the Basal ganglia.
Hippocampus is a part of brain, which forms one of the components of the Limbic system. It is responsible for forming ‘cognitive maps’ of information. Cognitive maps
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are mental maps by which multiple information is oriented with each other, for
example remembering street maps. Right sided hippocampus is responsible for special orientation and the left side for other contextual information. Studies have shown that damage to the Hippocampus can produce anterograde amnesia43, this means no new memory is formed. Therefore hippocampus has an important role to play in memory encoding. It is also involved in the slow process of conversion of short term memory to long term memory that is ‘memory consolidation’. ‘Episodic memory’ the type of memory that gives explicit description of actual events is also not possible without the hippocampus.
The Amygdala located below the hippocampus has a central nucleus that strongly responds to emotional stimuli, especially fear44. The Amygdala is responsible for encoding emotional memories and enhancing them. The memories associated with strong emotions like fear are more likely to be retained because of this enhancing aspect of the Amygdala. It also allows the short term memory to be consolidated into long term memory whenever an emotional aspect is associated with it45. The
amygdale allows emotions to influence the way memories are stored and processes them at a deeper level so they are more likely to withstand forgetting.
The Cerebellum generally responsible for co-ordination of motor activities is responsible for ‘procedural memories’46. Procedural memory involves learning and retaining fine motor skills like riding a bicycle or playing a musical instrument as
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opposed to ‘explicit memory’ which is a conscious memory. People who have
transient global amnesia may have short term or even long term memory loss but they are able to retain the procedural memories that is still play an instrument that they have learnt if the cerebellum is intact.
The basal ganglia are a group of nuclei located in the medial temporal lobe consisting of sub-thalamic nucleus, Substantia Nigra, Globus Pallidus, the ventral striatum and the dorsal striatum (putamen and caudate nucleus). The basal ganglia are involved in unconscious memory process like acquiring motor skills and implicit memory. The nucleus accumbens, a division of the ventral stria is responsible for drug memory47. The caudate nucleus is involved in the process of operant conditioning and plays a role in acquiring stimulus-response habits as well as solving sequential tasks48. The frontal lobe is very important in the co-ordination of information. It helps a person select memories that are most relevant to the current situation and co-ordinate it to form a working memory trace49. They are also involved in helping us remember what is to be done in the future, an aspect known as prospective memory.
Temporal lobe is involved in autobiographical memory50 and recognition
memory51. The later involves the capacity to identify an object that has been recently encountered. Damage to the temporal lobe can cause impairment in long term
memories.
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The chain of events in memory formation:
External/environmental stimulus.
Perceived by various sense organs eye, ear, nose, skin and tongue.
Taken to the respective centers in the brain
The process of encoding at the memory centers of the brain, integration of the emotional aspect and modification by past experiences.
Memory stored as short term memory.
Process of consolidation: the slow process of converting short term memory into long term memory.
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The formation of false memories:
The general understanding about memory is that it is some form of mechanized recorder that accurately documents and stores information. But this is not true, memory is prone for distortions and fallacy and sometimes far from the truth. The thing that compounds the problem is that any given person believes that his or her memory is accurate.
A false memory is a distorted or fabricated recollection of an event that did not happen. Our memories can be distorted by proactive or retroactive interference.
Proactive interference is when our memory is distorted by our earlier experiences and retroactive interference is when our memory is distorted by the things that we
experience later.
There are five mechanisms by which false memories are formed52. They are 1. Misinformation - when false information is deliberately given to a person and
despite the concerned person witnessing the truth, is lead to register a false event.
2. Misattribution – this happens when details of two separate events are combined together and formed a cohesive memory.
3. Fuzzy tracing – when people record events based on their interpretation of what happened rather than what actually happened.
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4. Emotion – strong emotions create vivid memories but those memories are not entirely accurate.
5. Inference – this is an error in memory reconstruction, gaps in memories are filled with items that seem to fit but may not be accurate.
Stress influencing memory:
Stress has got a substantial impact on memory encoding, storage and recall.
Stress releases certain hormones and neurotransmitters that affect the brain and when stress is accompanied by negative emotions the consequence is even dire.
Memories accumulated under stress are not just prone to inaccuracy but recall of such memories is associated with recall of the negative emotions responsible for the encoding of the said memories.
Delusional memories:
A delusion is a false belief that is held by a person in his mind despite strong evidence to the contrary. They commonly occur in the context of mental or neurological illness but are not specific for any particular disease or syndrome.
They are of diagnostic importance in psychotic disorders like Schizophrenia, psychotic depression and manic episode of bipolar disorder.
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The three main criteria for diagnosis of delusion as described by the psychiatrist Karl Jasper are
1. The certainty – the belief is held with absolute conviction.
2. The in corrigibility – the belief is not changeable by providing proof to the contrary or by a compelling counter argument.
3. The impossibility – the belief is so bizarre or patently untrue that it is implausible.
Delusional memory: this is a false memory about a past event, the memory may be entirely untrue in that the event never took place or it may be incorrect recollection of an actual event. The formation of false memories has been discussed above.
Being treated in an intensive care unit exposes the patients to numerable situations that are conducive for registering of false memories. The patients are not conscious most of the time, they are unable to communicate either with the medical and paramedical staff or their relatives, they are not fully aware of the nature of their illness or their treatment and they are receiving sedative drug that either subject them to vivid dreams and nightmares that indistinguishable from reality or interfere with understanding of the surroundings and memory encoding.
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The types of delusions can be described based on theme53, the following are a few common delusions.
Delusion of control: there is a false belief that other people or external forces have control over ones thoughts, feelings or actions. Thought broadcast, thought
insertion and thought withdrawal are also examples of delusions of control.
Nihilistic delusions: the belief of nonexistence of parts of self or self or the external world, these patients are prone to believe that the world is ending.
Delusion of infidelity: the person firmly believes that one’s spouse is having an affair and this stems from pathological jealousy.
Delusion of guilt: a person believes that one has committed a crime or believes that he or she is responsible for some natural disaster.
Delusion of reference: the false belief that people or even inanimate objects around them have some hidden meaning. They may also believe that a news anchor is sending a message and communicating with them.
Erotomania: the patient believes that some other person usually of higher social status is in love with them.
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Grandiose delusion: an individual has an inflated opinion about oneself and believes that he or she has some special powers or has done something very important and has not received sufficient recognition for the same.
Religious delusion: a delusion with religious content usually combined with other form of delusion.
Somatic delusion: there is a false belief that the body is infected, or has disease or something abnormal.
Persecutory delusion54: these are the most common types of delusions. The person believes that he or she is being persecuted. They have three specific clinical
elements.
1. The person thinks that harm is occurring or going to occur.
2. The person thinks that the persecutor has intention to cause harm.
3. The person thinks that they are constantly being judged or profiled.
The patients believe that harm is being caused to them, they are being followed, spied upon or otherwise obstructed from pursuit of their goals. To the doctor treating the patient these systems of beliefs are so broad and complex that they can explain everything happening to a patient.
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Post-traumatic stress disorder(PTSD):
Definition: It is a condition of persistent and emotional stress occurring as a result of injury or severe psychological shock, typically involving disturbance of sleep and constant vivid recall of experience, with diluted response to others and the outside world.
The earliest description of post traumatic stress disorder can be found in Shakespeare’s ‘Henry IV’, a very accurate description of the symptom
constellation of PTSD can be found in Lady Percy’s soliloquy. During the first world around 1914 was soldiers exposed to artillery shelling complained of
symptoms like tinnitus, dizziness, headache, tremors, amnesia and hypersensitivity to noise. Although these symptoms suggest that there is some neurological damage no brain damage was found in these patients. These symptoms were linked to the explosions of artillery shelling and thus the term ‘shell shocked’, a precursor to the term PTSD was born. By the Battle of Passchendaele in 1917 the symptoms of shell shock was well recognized and soldiers who exhibited these symptoms were given time away from active battle duty and if the symptoms did not resolve they were moved to psychiatric centers for further treatment. Most of our modern understanding of PTSD is by studying war sufferers during the Vietnam war and the term ‘post traumatic stress disorder was officially recognized in the year 1980.
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Causes of PTSD:
PTSD can be caused by exposure of a person to a traumatic event. A traumatic event is an experience that can cause physical, psychological or emotional distress. The event could be perceived as a threat to ones safety or stability.
The common events that when exposed to can cause55 PTSD are
1. Natural disasters such as floods, forest fires, earthquakes and tsunamis.
2. Being in or witnessing a serious road traffic accident.
3. Being exposed to sexual or physical abuse.
4. Witnessing or being a part of community violence like mugging, burglary, murder or bullying.
5. Sudden or unexpected death of someone close.
6. Experiencing a serious injury, major surgery or life threatening illness.
7. Being a victim of or participating in war.
8. Victims of terrorism.
9. Domestic violence.
10. Work related PTSD is common in journalists, health care workers, police men, fire and emergency service workers.
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The epidemiology56 of PTSD:
The majority of the population experiences at least one traumatic event in the lifetime, but the lifetime prevalence of PTSD is 10.4% for women and 5% for men.
Men tend to experience more traumatic events than women but women experience more events that are likely to lead to PTSD. Intentional acts of violence are more likely to lead to PTSD than natural disasters.
Symptoms of PTSD:
Words, objects or events in day to day life or even persons own thoughts can act as a trigger to re-experiencing symptoms. They include flashbacks of the event, nightmares and frightening thoughts.
The person may develop avoidance to the things or places that remind them of the event. Staying away from places, events or objects, feeling emotionally numb, feeling worry, depression or strong guilt losing interest in activities that were enjoyable in the past and unable to remember the dangerous event are all avoidance symptoms.
Unlike the above symptoms Hyper-arousal symptoms do not need a trigger, they are constantly present and are a major hindrance to day-to-day activities. It is a major cause for stress and anger in patients. The Hyper-arousal symptoms are
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being easily startled, feeling on the ‘edge’ and having difficulty sleeping and having anger outbursts.
These symptoms can be seen in all people who experience a traumatic event, but these serious symptoms do not last for more than a few weeks, I such cases the condition is called acute stress disorder (ASD). If the symptoms last more than a few weeks and up to three months then we call it Acute PTSD. But if the
symptoms persist beyond three months then PTSD is said to have become chronic.
Pathophysiology56 of PTSD:
Sufferers of PTSD have abnormally low levels of serum cortisol, and there seems to be hyper suppression of cortisol secretion to low doses of dexamethasone.
The pattern of abnormality in the Hypothalamo-pituitary-adrenal axis suggests that this axis may have an enhanced negative feedback. Other neuro-chemical
abnormalities that might include sensitization of nor adrenergic and the
serotonergic systems and involvement of the endogenous opioids, but evidence to these hypothesis is largely lacking.
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Diagnostic criteria for PTSD:
Recently, in June 2013 the American Psychiatric association has revised and published the diagnostic criteria for PTSD in Diagnostic and Statistical manual of Mental disorders-fifth edition (DSM-5). Please refer to the appendix for the
diagnostic criteria.
Well validated structured clinical interviews are available for diagnosis based on DSM-4 but they are yet to be updated for DSM-5.
Post traumatic stress disorder and health related quality of life in patients who have had ICU experience:
Critical illness and their therapies expose patients to extreme stressors, including respiratory insufficiency, pain and discomfort with endotrachial
intubation and suctioning, release of inflammatory cytokines, undue strain on the hypothalamic-pituitary-adrenal axis administration of exogenous
catecholamines/inotropes and delirium with associated psychotic experiences and all this is compounded by the in ability to communicate and limitation of
autonomy1. ICU is a stressful and noisy environment with little differentiation between night and day57. Critical illnesses are also life threatening and many patients experience frightening experiences58.
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Extended follow up of survivors of ICU treatment has shown many patients suffer long term physical and psychological consequences that affect their quality of life59. One form of psychological morbidity, post traumatic stress disorder is increasingly reported in ICU survivors, and they suffer major impairments in health related quality of life in long term606162.
Risk factors for development of PTSD in intensive care patients:
Prior psychopathology, greater ICU benzodiazepine administration, and post ICU memories of in-ICU frightening and/or psychotic experiences.
Agitation while in the ICU64.
Use of physical restraint while in ICU65. Use of neuromuscular blocking drugs66.
Memory and PTSD after ICU stay:
Schelling and colleagues found that memories of adverse experiences while in ICU correlated with subsequent PTSD symptoms and were also related to poor general quality of life scores67.
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Jones et al in their study61 found that incidence of PTSD is high in patients with delusional memory, and the presence of factual memory protects against the development of PTSD. The study hypothesized that patients who are deeply sedated in ICU will have few or none factual recall of their ICU stay (external events) and will fill the gap of memory with internal events (delusions and hallucinations).
ICU memory tool:
This is a questionnaire used to document factual memories, unpleasant memories and delusional memories of the ICU stay. It is used as a tool to interview patients who have had a period of stay in the ICU. This tool has been validated by a study done by Jones c et al published in Clinical intensive care journal68. Kindly refer to the appendix for ICU memory tool.
