A case series of the Royal Perth Hospital cannula-first approach in the 'can't intubate, can't oxygenate' scenario.

At the Royal Perth Hospital, we have been developing and teaching a can't intubate, can't oxygenate (CICO) rescue algorithm for over 19 years, based on live animal simulation. The algorithm involves a 'cannula-first' approach, with jet oxygenation and progression to scalpel techniques if required in a stepwise fashion. There is little reported experience of this approach to the CICO scenario in humans. We present eight cases in which a cannula-first Royal Perth Hospital approach was successfully implemented during an airway crisis. We recommend that institutions teach and practice this approach; we believe it is effective, safe and minimally invasive when undertaken by clinicians who have been trained in it and have immediate access to the requisite equipment. The equipment is low cost, comprising a 14G Insyte cannula, saline, 5 ml syringe and a Rapid-O2. Training can be provided using low-fidelity manikins or part-task trainers.

Effect of Apneic Oxygenation on Tracheal Oxygen Levels, Tracheal Pressure, and Carbon Dioxide Accumulation: A Randomized, Controlled Trial of Buccal Oxygen Administration.

BACKGROUND: Apneic oxygenation via the oral route using a buccal device extends the safe apnea time in most but not all obese patients. Apneic oxygenation techniques are most effective when tracheal oxygen concentrations are maintained >90%. It remains unclear whether buccal oxygen administration consistently achieves this goal and whether significant risks of hypercarbia or barotrauma exist. METHODS: We conducted a randomized trial of buccal or sham oxygenation in healthy, nonobese patients (n = 20), using prolonged laryngoscopy to maintain apnea with a patent airway until arterial oxygen saturation (SpO2) dropped <95% or 750 seconds elapsed. Tracheal oxygen concentration, tracheal pressure, and transcutaneous carbon dioxide (CO2) were measured throughout. The primary outcome was maintenance of a tracheal oxygen concentration >90% during apnea. RESULTS: Buccal patients were more likely to achieve the primary outcome (P < .0001), had higher tracheal oxygen concentrations throughout apnea (mean difference, 65.9%; 95% confidence interval [CI], 62.6%-69.3%; P < .0001), and had a prolonged median (interquartile range) apnea time with SpO2 >94%; 750 seconds (750-750 seconds) vs 447 seconds (405-525 seconds); P < .001. One patient desaturated to SpO2 <95% despite 100% tracheal oxygen. Mean tracheal pressures were low in the buccal (0.21 cm·H2O; SD = 0.39) and sham (0.56 cm·H2O; SD = 1.25) arms; mean difference, -0.35 cm·H2O; 95% CI, 1.22-0.53; P = .41. CO2 accumulation during early apnea before any study end points were reached was linear and marginally faster in the buccal arm (3.16 vs 2.82 mm Hg/min; mean difference, 0.34; 95% CI, 0.30-0.38; P < .001). Prolonged apnea in the buccal arm revealed nonlinear CO2 accumulation that declined over time and averaged 2.22 mm Hg/min (95% CI, 2.21-2.23). CONCLUSIONS: Buccal oxygen administration reliably maintains high tracheal oxygen concentrations, but early arterial desaturation can still occur through mechanisms other than device failure. Whereas the risk of hypercarbia is similar to that observed with other approaches, the risk of barotrauma is negligible. Continuous measurement of advanced physiological parameters is feasible in an apneic oxygenation trial and can assist with device evaluation.

Massive Subcutaneous Emphysema and Bilateral Tension Pneumothoraces After Supplemental Oxygen Delivery via an Airway Exchange Catheter: A Case Report.

A patient suffered massive subcutaneous emphysema and bilateral tension pneumothoraces after receiving supplemental oxygen through an airway exchange catheter (AEC). Complications of AEC placement include misplacement, direct injury to the larynx, bronchi or lung, barotrauma related to oxygen supplementation, and a loss of airway. We review these complications and discuss the specific risks of supplementing oxygen using an AEC. We suggest measures to limit pressure from the oxygen source and warn against advancing an AEC too far into the tracheobronchial tree.

Gonadal steroids, gonadotropins and DHEAS in young adults with familial hypercholesterolemia who had initiated statin therapy in childhood.

OBJECTIVE: Statins are currently the preferred pharmacological therapy in children with familial hypercholesterolemia (FH) with the aim to prevent premature cardiovascular disease (CVD). However, concerns have been raised that lowering cholesterol levels with statins could interfere with hormone production. In this study hormone concentrations were assessed in young adult FH subjects before and 10 years after the initiation of statins, and compared with their unaffected siblings. METHODS: All 214 FH children (8-18 years) who were previously randomized into a placebo-controlled trial evaluating the 2-year efficacy and safety of pravastatin, and their 95 unaffected siblings, were eligible. Women using oral contraceptives were excluded. Fasted blood samples were taken to measure lipids and testosterone (males), estradiol (females), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and dehydroepiandosterone (DHEAS). RESULTS: After ten years, gonadal steroid and gonadotropin concentrations were within the reference interval and did not differ between FH subjects (n = 88) and unaffected siblings (n = 62). Mean DHEAS concentrations (±standard deviation) in the FH subjects and female siblings were normally distributed within the reference interval, whereas male siblings had a higher mean DHEAS concentration than their FH brothers (12.9 [± 4.9] vs. 8.4 [± 3.0] µmol/L, respectively, p < 0.0001). CONCLUSION: After ten years of statin treatment, testosterone, estradiol, LH and FSH concentrations in young adult FH patients are within the reference interval and comparable to their unaffected siblings. These results strengthen current guidelines that statins in FH subjects could be safely used from childhood onwards to prevent premature CVD.

Long-term statin treatment in children with familial hypercholesterolemia: more insight into tolerability and adherence.

BACKGROUND: Statins are currently the preferred pharmacological therapy in individuals with familial hypercholesterolemia (FH) with the aim to prevent premature atherosclerosis. In adults, these agents have been proven to be safe and well tolerated; however, non-adherence is a significant clinical issue. OBJECTIVES: In this study, we evaluated tolerability and adherence to statin therapy in young adult FH patients 10 years after this was initiated in their childhood. METHODS: A questionnaire including items on medical history, adherence and reasons for discontinuation was sent to 214 young adult FH patients that initiated statin therapy at least 10 years ago. Tolerability was defined as 100% minus the percentage of patients that discontinued statin therapy due to side effects. Adherence was defined as the extent to which patients took their medication as prescribed by their physician. We labelled patients adherent if they took 80% or more of their pills in the month preceding our assessment. RESULTS: Follow-up was successful in 205 (95.8%) subjects (age 18-30 years). A history of side effects was reported by 40 (19.5%) of the patients, and mainly consisted of muscle complaints and gastrointestinal symptoms. Three patients (1.5%) discontinued statin therapy because of side effects. Rhadbomyolysis or other serious adverse events were not reported. In fact, 169 (82.4%) of 205 patients remained on statin treatment and 78.7% (148 out of 188) were adherent. None of the patient characteristics were significantly associated with adherence. CONCLUSIONS: Individuals with FH who started statin therapy in childhood demonstrated good adherence during ten years of treatment. Furthermore, statin therapy was well tolerated; only a small minority discontinued therapy because of side effects and the side effects that were reported were mild in nature.

Inheritance pattern of familial hypercholesterolemia and markers of cardiovascular risk.

Studies in children and adults have resulted in conflicting evidence in the quest for the answer to the hypothesis that offspring from hypercholesterolemic mothers might have an increased cardiovascular risk. Previous studies might have suffered from limitations such as cohort size and clinical sampling bias. We therefore explored this hypothesis in large cohorts of both subjects with familial hypercholesterolemia (FH) and unaffected siblings in a wide age range. In three cohorts (cohort 1: n = 1,988, aged 0-18 years; cohort 2: n = 300, 8-30 years; cohort 3: n = 369, 18-60 years), we measured lipid and lipoproteins as well as carotid intima-media thickness (c-IMT) in offspring from FH mothers versus FH fathers. For LDL cholesterol, triglycerides (TGs), and c-IMT, we performed a pooled analysis. No significant differences could be observed in c-IMT, lipid, or lipoprotein levels from offspring of FH mothers versus FH fathers. Pooled analyses showed no significant differences for either LDL cholesterol [mean difference 0.02 (-0.06,0.11) mmol/l, P = 0.60], TGs [mean difference 0.07 (0.00,0.14) mmol/l, P = 0.08], or c-IMT [mean difference -0.00 (-0.01,0.01) mm, P = 0.86]. Our data do not support the hypothesis that cardiovascular risk markers are different between offspring from FH mothers and FH fathers.

[Metamizole in postoperative pain management]. / Metamizol bij postoperatieve pijnbestrijding.

Postoperative pain management is an essential part of surgical management. In the Netherlands paracetamol, NSAIDs and, if necessary, opioids are the most commonly used drugs for perioperative analgesia. Metamizole is a non-opioid analgesic that is rarely used in the Netherlands, although it is one of the most frequently used analgesics around the world. Metamizole is registered in the Netherlands for intravenous therapy for acute pain. However, the drug has been rarely used since the 1970s because of what was thought to be an unacceptable risk of agranulocytosis. Recent scientific data do not justify this reasoning. Its mechanism of action is still under discussion, but the main action is likely to be an inhibition of prostaglandin synthesis in both peripheral tissues and the central nervous system. Based on the current literature, metamizole deserves a role in the management of post-operative pain in the Netherlands. It seems to be a safe and effective drug for acute pain management especially when compared with NSAIDs.

Follow-up of children diagnosed with familial hypercholesterolemia in a national genetic screening program.

OBJECTIVE: To assess the follow-up of children diagnosed as having familial hypercholesterolemia (FH) in the nationwide DNA-based cascade screening program (the Netherlands). STUDY DESIGN: Questionnaires covering topics such as demographics, family history, physician consultation, and treatment were sent to parents of patients with FH (age 0-18 years), 18 months after diagnosis. RESULTS: We retrieved 207 questionnaires of patients aged 10.9 ± 4.2 years (mean ± SD) at diagnosis; 48% were boys, and the mean low-density lipoprotein cholesterol (LDL-C) level at diagnosis was 167 ± 51 mg/dL. Of these patients, 164 (79%) consulted a physician: a general practitioner (35%), lipid-clinic specialist (27%), pediatrician (21%), internist (11%), or another physician (6%). LDL-C level at diagnosis and a positive family history for cardiovascular disease were independent predictors for physician consultation. Of the patients who visited a physician, 62% reported to have received lifestyle advice, and 43 (26%) were prescribed statin treatment. Independent predictors for medication use were age, LDL-C level, and educational level of parents. CONCLUSION: The follow-up of children with FH after diagnosis established through cascade screening is inadequate. Better education of patients, parents, and physicians, with a structured follow-up after screening, should improve control of LDL-C levels and hence cardiovascular risk in children with FH.

Molecular basis of autosomal dominant hypercholesterolemia: assessment in a large cohort of hypercholesterolemic children.

BACKGROUND: Autosomal dominant hypercholesterolemia (ADH) is characterized by elevated low-density lipoprotein cholesterol levels and premature cardiovascular disease. Mutations in the genes encoding for low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) underlie ADH. Nevertheless, a proportion of individuals who exhibit the ADH phenotype do not carry mutations in any of these 3 genes. Estimates of the percentage of such cases among the ADH phenotype vary widely. We therefore investigated a large pediatric population with an unequivocal ADH phenotype to assess the molecular basis of hereditary hypercholesterolemia and to define the percentage of individuals with unexplained dyslipidemia. METHODS AND RESULTS: We enrolled individuals with low-density lipoprotein cholesterol levels above the 95th percentile for age and gender and an autosomal dominant inheritance pattern of hypercholesterolemia from a large referred pediatric cohort of 1430 children. We excluded children with thyroid dysfunction, nephrotic syndrome, autoimmune disease, liver disease, primary biliary cirrhosis, and obesity (body mass index >75th percentile for age and gender), as well as children referred via a cascade screening program and those from families with a known molecular diagnosis. Of the 269 children who remained after the exclusion criteria were applied, 255 (95%) carried a functional mutation (LDLR, 95%; APOB, 5%). CONCLUSION: In the vast majority of children with an ADH phenotype, a causative mutation can be identified, strongly suggesting that most of the large-effect genes underlying ADH are known to date.

Rosuvastatin lowers coenzyme Q10 levels, but not mitochondrial adenosine triphosphate synthesis, in children with familial hypercholesterolemia.

OBJECTIVE: To investigate whether statin therapy affects coenzyme Q10 (CoQ10) status in children with heterozygous familial hypercholesterolemia (FH). STUDY DESIGN: Samples were obtained at baseline (treatment naïve) and after dose titration with rosuvastatin, aiming for a low-density lipoprotein cholesterol level of 110 mg/dL. Twenty-nine patients were treated with 5, 10, or 20 mg of rosuvastatin for a mean period of 29 weeks. RESULTS: We found a significant (32%) decrease in peripheral blood mononuclear cell (PBMC) CoQ10 level (P = .02), but no change in PBMC adenosine triphosphate synthesis (P = .60). Uncorrected plasma CoQ10 values were decreased significantly, by 45% (P < .01). In contrast, ratios of plasma CoQ10/total cholesterol and CoQ10/low-density lipoprotein cholesterol remained equal during treatment. CONCLUSIONS: In children with FH, rosuvastatin causes a significant decrease in cellular PBMC CoQ10 status but does not affect mitochondrial adenosine triphosphate synthesis in children with FH. Further studies should address whether (rare) side effects of statin therapy could be explained by a deterioration in CoQ10 status.

Uremic thrombocytopathy is not about urea.

Platelet dysfunction in renal failure is attributable to high levels of small, partly dialyzable molecules known as uremic toxins, hence the term "uremic thrombocytopathy." Although a variety of moieties contribute to platelet dysfunction or abnormal interactions between platelets and the vascular wall, urea remains a potential factor. Here, we studied three family members with familial azotemia, a rare autosomal dominant syndrome characterized by high plasma urea resulting from impaired urinary excretion but normal renal function otherwise. Platelet function, assessed in vitro and by traditional bleeding time, was normal in all individuals. Abnormal platelet function in patients with renal failure is not caused by high concentrations of urea.

Efficacy and safety of rosuvastatin therapy for children with familial hypercholesterolemia.

OBJECTIVES: This study was undertaken to evaluate the efficacy and safety of rosuvastatin therapy for children with familial hypercholesterolemia. BACKGROUND: Familial hypercholesterolemia is a common inherited disorder causing markedly elevated low-density lipoprotein cholesterol (LDL-C) levels from birth and resulting in premature atherosclerosis. In children, statins have been shown to be effective in reducing LDL-C, restoring flow-mediated dilation, and slowing carotid intima-media thickening. However, few children in these trials achieved current LDL-C goals. METHODS: This study comprised a 12-week double-blind, randomized, placebo-controlled trial, followed by a 40-week open-label, titration-to-goal extension phase in 177 pubertal children, ages 10 to 17 years, with familial hypercholesterolemia. Participants were randomly assigned to placebo or rosuvastatin 5, 10, or 20 mg once daily. RESULTS: Compared with placebo, rosuvastatin 5, 10, and 20 mg reduced LDL-C by 38%, 45%, and 50%, respectively (p < 0.001 for each group vs. placebo). With a maximum allowed dose of 20 mg, 40% achieved the treatment goal of <110 mg/dl during the open-label, titration-to-goal phase. Rosuvastatin was well tolerated, with no apparent adverse impact on growth or development. CONCLUSIONS: In children with familial hypercholesterolemia, rosuvastatin 20 mg daily reduced LDL-C by 50%. Nonetheless, only 40% attained the consensus LDL-C target of <110 mg/dl, reflecting these patients' high baseline LDL-C levels (mean, 232 mg/dl). (Pediatric Lipid-Reduction Trial of Rosuvastatin [PLUTO]; NCT00355615).

Pregnancy in women suffering from familial hypercholesterolemia: a harmful period for both mother and newborn?

PURPOSE OF REVIEW: The present review aims to highlight the consequences for mother and child of profound hypercholesterolemia during pregnancy of women with familial hypercholesterolemia. RECENT FINDINGS: Familial hypercholesterolemia is increasingly diagnosed in younger patients due to the existence of screening programs and more widespread cholesterol testing. Increasing numbers of young female patients with familial hypercholesterolemia raise the issue of pregnancy and its consequences for the familial hypercholesterolemia patient herself but also for her offspring. When pregnancy is considered, lipid-lowering drugs are often discontinued because of the fear for teratogenic effects. The evidence for teratogenesis associated with statin use is scant and conflicting. On the other hand, several studies do suggest that pronounced hypercholesterolemia during pregnancy has adverse effects on both fetus and mother. In fact, human and animal studies reveal an enhanced tendency toward atherosclerosis in the offspring of women who suffer from hypercholesterolemia during pregnancy. In animal studies, some evidence exists that this can be reversed by treatment with lipid-lowering and antioxidative agents. Until today, however, no human studies exist that have evaluated efficacy or safety of lipid-lowering interventions in pregnant women with familial hypercholesterolemia. SUMMARY: Altogether, the suggested relationship between severe hypercholesterolemia and enhanced atherosclerosis in offspring and possibly the mother warrants further confirmation and, consequently, studies that focus on therapeutic strategies that can safely lower cholesterol levels during pregnancy in these women.

The use of lipid-lowering drug therapy in children and adolescents.

Atherosclerosis, the condition underlying cardiovascular disease (CVD), often begins in childhood. Therefore, strategies to prevent CVD should be implemented at an early age, especially in populations at high risk for CVD. In addition to lifestyle interventions, these strategies include pharmacological treatment of dyslipidemia, a well-established risk factor for CVD in adults. Several lipid-lowering agents have been evaluated in children; however, long-term safety and efficacy data are lacking. As in adults, statins are the preferred pharmacological agents in pediatric practice due to excellent efficacy and tolerability, with few adverse safety outcomes observed to date. Nevertheless, more studies are needed to confirm the lifelong benefit of lipid-lowering therapy initiated in childhood.

Efficacy and safety of coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia.

OBJECTIVES: The study evaluated the efficacy and safety of long-term coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia (HeFH). BACKGROUND: Aggressive intervention to achieve lipid goals for adolescents with HeFH is recommended to reduce risk of premature cardiovascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled study, 248 male and female subjects ages >or=10 and