Inborn oxidative phosphorylation defect as risk factor for propofol infusion syndrome

Propofol is an anesthetic agent widely used for induction and maintenance of anesthesia, and sedation in children. Although generally considered as reliable and safe, administration of propofol can occasionally induce a potentially fatal complication known as propofol infusion syndrome (PRIS). Mitochondrial dysfunction has been implicated in the pathogenesis of PRIS. We report on an adult patient with Leber hereditary optic neuropathy (LHON) who developed PRIS. He was a carrier of the m.3460G>A mutation, one of the major three pathogenic point mutations associated with LHON. The propositus was blind and underwent propofol sedation after severe head injury. Five days after start of propofol infusion, the patient died. The activity of complex I of the oxidative phosphorylation (OXPHOS) system was severely deficient in skeletal muscle. Our observation indicates that fulminate PRIS can occur in an adult patient with an inborn OXPHOS defect and corroborates the hypothesis that PRIS is caused by inhibition of the OXPHOS system.     

Propofol infusion syndrome associated with short-term large-dose infusion during surgical anesthesia in an adult

In this case report we describe a case of propofol infusion syndrome in an adult after a short-term infusion of large-dose propofol during a neurosurgical procedure. Large-dose propofol (9 mg.kg(-1).h(-1)) was given for only 3 h during surgery and was followed by a small-dose infusion (2.3 mg.kg(-1).h(-1)) for 20 h postoperatively. The patient had also received large doses of methylprednisolone. He developed a marked lactic acidosis with mild biological signs of renal impairment and rhabdomyolysis but no cardiocirculatory failure. There were no other evident causes of lactic acidosis as documented by laboratory data. We believe this is the first report of reversible lactic acidosis associated with a short duration of large-dose propofol anesthesia.     

Short-term low-dose propofol anaesthesia associated with severe metabolic acidosis

Propofol-induced metabolic acidosis is well recognised in the paediatric literature, but the existence of such a syndrome in adults remains contentious. In most reported cases, metabolic acidosis complicated prolonged administration of propofol in critically ill patients. We present a case of severe non-fatal reversible metabolic acidosis, without ventilatory depression or hypoxia, related to short-term propofol infusion in an adult during and after coronary artery bypass grafting. We suggest that lactic acidosis occurred in a genetically susceptible patient with an abnormality of mitochondrial function. This report discusses an unusual adverse effect of propofol anaesthesia and sedation and highlights the need for further investigation to define propofol toxicity.     

Clinical management of cardiogenic shock associated with prolonged propofol infusion

This case report details the development of cardiogenic shock after craniotomy in a patient sedated with a propofol infusion. The patient survived with the assistance of extracorporeal membrane oxygenation. A literature review summarizes the syndrome of cardiogenic shock associated with prolonged propofol infusion. This is the first report of survival in this syndrome resuiting from mechanical circulatory support.     

Total intravenous anesthesia for repositioning an implantable defibrillator in a patient with long QT syndrome

We report the case of a 27-year-old woman with congenital long QT syndrome (LQTS) who was scheduled for surgery to reposition an implantable defibrillator. Given the risk of sudden death due to fatal ventricular arrhythmia, the woman required implantation of a defibrillator with pacemaker capability. Combined anesthesia-analgesia was used in order to minimize the risk of ventricular arrhythmia caused by increased serum concentrations of catecholamines. When cardioversion, defibrillation and anti-tachycardia functions had been deactivated, anesthesia was induced with propofol, fentanyl and rocuronium. Anesthesia was maintained with an infusion of propofol and remifentanil. We describe the pathophysiology and treatment of LQTS and discuss anesthetic management for repositioning a defibrillator in a patient with congenital LQTS.     

Propofol infusion syndrome in a patient with sepsis

Propofol is widely used for sedation in critically ill patients. Several adult patients, all with acute neurological disorders, have been reported suffering from propofol infusion syndrome, which occurs in patients receiving high-dose propofol and catecholamines and/or steroids. We present a case of a septic patient without neurological illness who developed propofol infusion syndrome.     

Propofolinfusionssyndrom

The propofol infusion syndrome is a rare but potentially lethal complication resulting from a prolonged continuous administration of propofol. It was first described in the beginning of the 1990's and in recent years there have been frequent reports of problems in association with the use of propofol sedation. The cardinal signs and symptoms of the propofol infusion syndrome are metabolic acidosis, rhabdomyolysis, renal failure, cardiac arrhythmias and a progressive, often therapy-resistant cardiac failure. The pathophysiology of this syndrome appears to involve a disturbance of mitochondrial metabolism induced by propofol. Our report involves a case of propofol infusion syndrome in a patient having undergone cardiac surgery.     

Death after re-exposure to propofol in a 3-year-old child: a case report

This case report discusses the cause of death in a 3-year-old child who survived a high dose (20 mg x kg-1 x h-1) of propofol, infused over a period of 15 h, following which the patient developed a combined respiratory and metabolic acidosis, the oxygenation remaining normal. Bronchospasm was assumed to be the cause of hypercapnia. At this time the doctors in charge did not think of a possible side-effect of propofol. The administration of propofol was interrupted, the patient recovered within 13 h from the acidosis, woke up and required further sedation. A supposedly entirely safe infusion of 4 mg x kg-1 x h-1 propofol, as recommended in the literature for up to 48 h, was administered. After only 8 h intractable bradycardic dysrhythmias occurred. Although pharmacokinetic studies have pointed to a possible accumulation of propofol during continuous infusions, an interruption of an infusion for several hours has been considered sufficient for practically total clearance of the drug from the body. In this case re-exposure with a recommended dose of propofol was accompanied by bradycardia and dysrythmias that proved to be resistant to therapy and led to fatal cardiac insufficiency with a functioning artificial pacemaker in place. This case raises concerns about the safety of long-term infusions of propofol for sedation in children and possibly also in adults.     

Propofol infusion syndrome

Propofol infusion syndrome has not only been observed in patients undergoing long-term sedation with propofol, but also during propofol anesthesia lasting 5 h. It has been assumed that the pathophysiologic cause is propofol's impairment of oxidation of fatty acid chains and inhibition of oxidative phosphorylation in the mitochondria, leading to lactate acidosis and muscular necrosis. It has been postulated that propofol might act as a trigger substrate in the presence of priming factors. Severe diseases in which the patient has been exposed to high catecholamine and cortisol levels have been identified as trigger substrates. Once the development of propofol infusion syndrome is suspected, propofol infusion has to be stopped immediately and specific therapeutic measures initiated, including cardiocirculatory stabilization and correction of metabolic acidosis. To increase elimination of propofol and its potential toxic metabolites, hemodialysis or hemofiltration are recommended. Due to its possible fatal side effects, the use of propofol for long-term sedation in critically ill patients should be reconsidered. In cases of unexplained lactate acidosis occurring during continuous propofol infusion, propofol infusion syndrome must be taken into consideration.     

Propofol-Infusionssyndrom

Propofol infusion syndrome has not only been observed in patients undergoing long-term sedation with propofol, but also during propofol anesthesia lasting 5 h. It has been assumed that the pathophysiologic cause is propofol’s impairment of oxidation of fatty acid chains and inhibition of oxidative phosphorylation in the mitochondria, leading to lactate acidosis and muscular necrosis. It has been postulated that propofol might act as a trigger substrate in the presence of priming factors. Severe diseases in which the patient has been exposed to high catecholamine and cortisol levels have been identified as trigger substrates. Once the development of propofol infusion syndrome is suspected, propofol infusion has to be stopped immediately and specific therapeutic measures initiated, including cardiocirculatory stabilization and correction of metabolic acidosis. To increase elimination of propofol and its potential toxic metabolites, hemodialysis or hemofiltration are recommended. Due to its possible fatal side effects, the use of propofol for long-term sedation in critically ill patients should be reconsidered. In cases of unexplained lactate acidosis occurring during continuous propofol infusion, propofol infusion syndrome must be taken into consideration.     

Lactic acidosis associated with propofol during general anaesthesia for neurosurgery

Propofol infusion syndrome (PRIS) is a new clinical entity reported in critically ill patients. Lactic acidosis, cardiac failure and rhabdomyolysis are the features. Lactic acidosis related to short-term propofol administration has been described during general anaesthesia. Lactic acidosis could be an early marker of PRIS. We report here a case of very early lactic acidosis in a 66-year-old-man receiving propofol during a neurosurgery. The outcome was good after discontinuation of propofol.     

Use of propofol infusion in Australian and New Zealand paediatric intensive care units

Despite the risk of propofol infusion syndrome, a rare but often fatal complication of propofol infusion in ventilated children and possibly adults, propofol infusion remains in use in paediatric intensive care units (PICU). This questionnaire study surveys the current pattern of use of this sedative infusion in Australian and New Zealand PICUs. Thirty-three of the 45 paediatric intensive care physicians surveyed (73%), from 12 of the 13 intensive care units, returned completed questionnaires. The majority of practitioners (82%) use propofol infusion in children in PICU, the main indication being for short-term sedation in children requiring procedures. 39% of respondents consider propofol infusion useful in ventilated children requiring longer-term sedation. 67% of paediatric intensivists use maximum infusion doses that may be considered dangerously high (> or = 10 mg/kg/h). Nineteen per cent use propofol infusion for prolonged periods (> 72 hours). A smaller proportion (15%) of respondents indicate that they may use both higher doses and prolonged periods of infusion, a practice likely to lead to a greater chance of serious adverse events. Knowledge of local protocols for the use of propofol infusion is associated with a significantly greater level of monitoring for possible adverse events. We suggest that national guidelines for the use of propofol infusion in children should be developed. These should include clear indications and contraindications to its use, a maximum dose rate and maximum period of infusion, with a ceiling placed on the cumulative dose given and clearly stated minimum monitoring requirements.     

Grass‐green urine from propofol infusion

Green urine from propofol infusion is a benign and rare side effect. The discolouration appears when clearance of propofol exceeds hepatic elimination, and extrahepatic elimination of propofol occurs. This case report presents a 24‐year‐old male with grass green discolouration of urine based on propofol infusion.     

Late-onset pulmonary edema due to propofol

Pulmonary edema after the administration of propofol has rarely been reported. In this case report, we describe pulmonary edema due to the administration of propofol during a Cesarean section and while in the intensive care unit. The skin tests demonstrated strong positive weal and flare reactions to propofol. The patient was treated successfully with mechanical ventilatory support. This report emphasizes that this fatal complication may be seen with propofol and underlying mechanisms and therapeutic approach are discussed.     

Propofol for electrical storm; a case report of cardioversion and suppression of ventricular tachycardia by propofol

PURPOSE: To present a case report where propofol abolished recurrent ventricular tachycardia (VT) and to suggest a mechanism by which this may have occurred. Clinical features: A 65-yr-old male was admitted to the intensive care unit (ICU) with electrical storm. Recurrent episodes of VT persisted despite maximal anti-arrhythmic therapy and resulted in a prolonged ICU course and the need for intra-aortic balloon pump support. This was complicated by an ischemic limb, necessitating an anesthetic for femoral thrombectomy. On several occasions while in the ICU, episodes of VT had resolved with boluses of propofol prior to planned cardioversion. In the operating room, episodes of non-sustained VT resolved after a bolus of propofol and remained suppressed for the duration of the case with the use of a propofol infusion. CONCLUSION: The effects of propofol on cardiac conduction and on the autonomic nervous system have been studied but its effects on arrhythmias are not well documented. In this case report, propofol was associated with the resolution and suppression of VT. Recent evidence suggests that sympathetic blockade may be an effective treatment for electrical storm. This may be the mechanism by which propofol can abolish this arrhythmia intraoperatively.     

Compartment syndrome caused by a properly functioning infusion pump

Compartment syndrome caused by an infiltrated intravenous catheter has been previously reported, but there are no reports of compartment syndrome caused by fluids and/or medications dispensed by a properly functioning drug infusion pump. A case in which a commonly used drug infusion pump delivered propofol and remifentanil under high pressure, leading to compartment syndrome, is presented.     

Paediatric total intravenous anaesthetic use: a nationwide study

Introduction: Propofol is widely used for induction and maintenance of anaesthesia in paediatric patients. Following the initial reports of deaths following prolonged high dose infusions on intensive care (1), the propofol infusion syndrome was described (2). The exact cause of this is still uncertain but consistent biochemical abnormalities have been described (3, 4). Initially the cases were all in children on intensive care units, but more recently cases have been reported in adults. Of greater concern to paediatric anaesthetists are the reports of deaths following propofol infusions in theatre (5, 6). We set out to define the current use of propofol infusions by Paediatric Anaesthetists within the UK. Methods: A list of names and addresses of paediatric anaesthetists was composed by contacting anaesthetic departments at the hospitals by telephone and asking for the names of their paediatric anaesthetists. An 18 question survey with an enclosed stamped, addressed envelope was posted to 388 consultant paediatric anaesthetists in 51 hospitals throughout the UK. The survey was re‐submitted once to consultants who had not initially replied. The results were tabulated onto a database and analysed. Results: We received a total of 242 replies (63% of surveyed population), 240 of which regularly anaesthetised children. Within the last year 13% had used propofol infusions on children under 1, 31% in children 1–5 years, 41% in children 5–10 years and 46% in the over 10 s. The two most common surgical specialties with which propofol TIVA was used were ENT (n = 66), and orthopaedics (n = 53), the most common operations stated being middle ear surgery, muscle biopsy and scoliosis surgery. The reasons for using propofol in these patients were broad and included both anaesthetic and surgical considerations. 60 consultants questioned used propofol infusions in children at least monthly, 98 rarely and 72 never. Over 50% of replies believed that propofol infusions reduced the rate of postoperative nausea and vomiting in respect to inhalational techniques, less agreed that there was faster recovery time or time to discharge. Remifentanil was commonly used with propofol infusions but target controlled infusion devices were uncommonly used. The longest time anyone considered using propofol for was 72 h, although the mode of all positive responses was 6 h. The majority of people failed to give a maximum infusion rate. Conclusions: Propofol infusions are used widely throughout the UK for their perceived anaesthetic and surgical benefits. Given that there are well documented catastrophic, albeit rare side effects, it is surprising that there are no guidelines for infusions in theatre. Further work is required to elucidate the exact mechanism of propofol infusion syndrome to guide future anaesthetic practice. References 1 Parke TJ, Stevens JE, Rice AS et al. Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports. Br Med J 1992; 305 : 613–616. 2 Bray RJ. Propofol infusion syndrome in children. Paediatr Anaes 1998; 8 : 491–499. 3 Wolf AR, Weir P, Segar P, et al. Impaired fatty acid oxidation in propofol infusion syndrome. Lancet 2001; 357 : 606–607. 4 Wolf AR, Potter F. Propofol infusion in children: when does an anesthetic tool become an intensive care liability? Paediatr Anaesth 2004; 14 : 435–438. 5 Mehta N, DeMunter C, Habibi P et al. Short‐term propofol infusions in children. Lancet 1999; 354 : 866–867. 6 Kill C, Leonhardt A, Wulf H. Lacticacidosis after short‐term infusion of propofol for anaesthesia in a child with osteogenesis imperfecta. Paediatr Anaesth 2003; 13 : 823–826.     

Kataraktoperation bei einem Patienten mit schwerem obstruktivem Schlafapnoesyndrom

This case report describes airway management during cataract surgery for a patient with known severe obstructive sleep apnea syndrome. Surgery could not be performed using a pure local anesthetic procedure because of the psychological history of the patient. In consideration of the severity of the patient's sleep apnea syndrome, we chose an anesthetic procedure that would compromise the upper airway as little as possible. For respiratory strategy, the patient's own nasal CPAP (continuous positive airway pressure) equipment was used. Anesthesia was maintained with continuous infusion of propofol and remifentanil while the patient was breathing spontaneously. The patient was transferred to the recovery room where nasal CPAP was continued for 1 h until the patient was returned to the ward.     

Hyperkalemia during surgery: is it an early warning of propofol infusion syndrome?

We present a case of severe hyperkalemia in a 48-year-old man after short-term infusion of an average dose of propofol. We suspected that the hyperkalemia in this patient was a sign of propofol infusion syndrome. The patient was undergoing a video-assisted esophagectomy, for which one-lung ventilation, with air/oxygen, isoflurane, and continuous epidural analgesia was supplemented with propofol infusion. In the intraoperative period, the patient developed severe hyperkalemia with mild acidosis but no cardiovascular failure. There were no other evident causes of hyperkalemia as documented by laboratory data. The procedure was abandoned and the patient was taken to postoperative recovery, where his potassium levels returned to normal at the end of 10 h.     

The propofol infusion 'syndrome' in intensive care unit: from pathophysiology to prophylaxis and treatment

Propofol is a short-acting intravenous anesthetic agent widely used for sedation in anesthesia and intensive care. However, during the last 15 years there have been quite a lot of publications reporting unexplained deaths among pediatric and adult critically ill patients. These cases shared common symptoms and signs unrelated with initial admission diagnosis and were under long-term propofol infusion at high doses. A new syndrome called 'propofol infusion syndrome' was defined, including cardiovascular instability, metabolic acidosis, hyperkalaemia and rhabdomyolysis, with no evidence for other known causes of myocardial failure. One common denominator in these patients was the presence of hypoxia and tissue hypoperfusion. It seems that during states of increased metabolic demand, the reduced energy production related to an inhibitory propofol action at the level of mitochondrial oxidative phosphorylation and lipid metabolism may lead to the manifestation of the syndrome. Furthermore, cases of early toxicity due to failure in cellular energy production with development of lactic acidosis have been also described during anesthesia. For the above reasons, recommendations for the limitation of propofol use have been devised by various institutions, whereas physicians need to be cautious when using prolonged propofol sedation and alert for early signs of toxicity.