Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord. PATIENTS AND METHODS: This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV). RESULTS: We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days. CONCLUSIONS: Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.

Caudal anesthesia for minor pediatric surgery: a prospective randomized comparison of ropivacaine 0.2% vs levobupivacaine 0.2%.

BACKGROUND: Previous published data comparing ropivacaine 0.2% with levobupivacaine 0.25% have suggested that ropivacaine might be associated with less early postoperative motor blockade compared with levobupivacaine. The aim of the present study was to further investigate this issue comparing equal concentrations (0.2%) of ropivacaine and levobupivacaine in children undergoing minor subumbilical surgery. METHODS: Following induction of a standardized anesthetic, patients (1-7 years) were randomized in a double-blind manner to receive a caudal block with either ropivacaine 0.2% (group R, n=30) or levobupivacaine 0.2% (group L, n=30), total volume 1 ml.kg-1. Motor blockade (modified Bromage scale; primary end-point) and analgesia [Children and Infants Postoperative Pain Scale (CHIPPS) score] were assessed at predetermined time points during the first 24-postoperative hours. RESULTS: Motor blockade was only registered during the first postoperative hour with no significant differences between the groups (group R n=5, group L n=8). Postoperative CHIPPS scores were almost identical in both groups with only seven and six patients requiring supplemental analgesia (CHIPPS score>or=4) in the R and L groups, respectively. CONCLUSIONS: A 0.2% concentrations of ropivacaine or levobupivacaine are clinically very similar with regard to postoperative analgesia and unwanted postoperative motor blockade in children undergoing minor subumbilical surgery.

Spinal versus peripheral effects of adjunct clonidine: comparison of the analgesic effect of a ropivacaine-clonidine mixture when administered as a caudal or ilioinguinal-iliohypogastric nerve blockade for inguinal surgery in children.

BACKGROUND: The adjunctive use of clonidine to local anaesthetics has been reported to enhance analgesia both after spinal and peripheral administration. However, no attempt has been made to compare spinal and peripheral application of clonidine in the same surgical context in order to further explore the mechanism for the analgesic action of clonidine when administered together with local anaesthetics. METHODS: Using a prospective, randomized, observer-blinded study design, 40 patients, aged 1-7 years, who were undergoing elective surgery for inguinal hernia repair or orchidopexy, were randomly allocated to receive either a caudal block (group C: n = 20; ropivacaine 0.2%, 1 ml.kg-1 + clonidine 2 micro g.kg-1) or an ilioinguinal-iliohypogastric nerve block (group I: n = 20; ropivacaine 0.2%, 0.4 ml.kg-1 + clonidine 2 micro g.kg-1) following the induction of a standardized sevoflurane based anaesthetic. Postoperative analgesia [maximum Objective Pain Scale (OPS) score and requirement for supplemental analgesia] and sedation (three-point scale) were assessed at predetermined intervals during the first 24 h postoperatively. RESULTS: Fourteen children in group I and nine children in group C did not require rescue analgesia (P = 0.17). No difference in maximum OPS scores could be detected between the two study groups. The mean time to full recovery regarding sedation was 149 min and 153 min in groups C and I, respectively. CONCLUSIONS: This pilot study demonstrates a trend for better postoperative analgesia following peripheral administration of clonidine compared with central application. However, the main mechanism for the adjunct analgesic effect of clonidine when administered together with local anaesthetics requires further study.

New drugs, new techniques, new indications in pediatric regional anesthesia.

The use of regional anesthesia in children represents one of the most effective methods for perioperative analgesia and postoperative pain control. Things have been dramatically changed in the last two decades due to the appearance of new safer drugs and new tools; moreover new techniques were introduced showing their efficacy. In this paper we briefly describe the efficacy of new local anesthetics and adjuvants; we review the use of continuous peripheral blocks and other not very diffused techniques of regional anesthesia.

How to prolong postoperative analgesia after caudal anaesthesia with ropivacaine in children: S-ketamine versus clonidine.

BACKGROUND: The aim of the study was to determine whether caudal S-ketamine or clonidine prolonged analgesia together with ropivacaine. METHODS: Sixty-three boys, aged 1-5 years, who were undergoing minor surgery, were allocated in order to receive one of three solutions for caudal anaesthesia. Group R received 2 mg x kg(-1) 0.2% ropivacaine; group C, 2 mg x kg(-1) 0.2% ropivacaine + clonidine 2 microg x kg(-1); and group K, 2 mg x kg(-1) 0.2% ropivacaine + S-ketamine 0.5 mg x kg(-1). RESULTS: Postoperative analgesia assessed by CHEOPS lasted 701 min in group K (P < 0.05) compared with 492 min in group C and 291 min in group R. There were no significant differences between the groups for incidence of haemodynamic and respiratory alterations, motor block or sedation. CONCLUSIONS: This study demonstrates that S-ketamine 0.5 mg x kg(-1) when added to 0.2% caudal ropivacaine provides better postoperative analgesia than clonidine without any clinically significant side-effect.

The dose-response relationship for clonidine added to a postoperative continuous epidural infusion of ropivacaine in children.

UNLABELLED: Epidurally administered clonidine enhances the quality and duration of postoperative analgesia when it is used as an adjunct to local anesthetics in children. We investigated the dose-response relationship for epidural clonidine when added to a continuous postoperative epidural infusion of ropivacaine. By use of an observer-blinded design, 55 pediatric patients (1-4 yr old) were randomly given a postoperative epidural infusion of plain ropivacaine 0.1% 0.2 mg. kg(-1). h(-1) (Group R), ropivacaine 0.08% 0.16 mg. kg(-1). h(-1) plus clonidine 0.04 microg. kg(-1). h(-1) (Group RC1), ropivacaine 0.08% 0.16 mg. kg(-1). h(-1) plus clonidine 0.08 microg. kg(-1). h(-1) (Group RC2), or ropivacaine 0.08% 0.16 mg. kg(-1). h(-1) plus clonidine 0.12 microg. kg(-1). h(-1) (Group RC3). A clear dose-response relationship could be identified for a continuous infusion of epidural clonidine, with clonidine dosages in the 0.08-0.12 microg. kg(-1). h(-1) range providing improved postoperative analgesia (reduced Children's Hospital of Eastern Ontario pain score, increased time to first supplemental analgesic demand, and a reduced total number of doses of supplemental analgesics during the first 48 h after surgery). Analgesia was improved without any signs of increased sedation or other side effects. The adjunct use of epidural clonidine in the dosage range of 0.08-0.12 microg. kg(-1). h(-1) appears effective and safe for use in children. IMPLICATIONS: The addition of clonidine (0.08-0.12 microg.kg(-1).h(-1))to a continuous epidural infusion of ropivacaine was found to improve postoperative pain relief in children. No clinically significant signs of sedation or other side effects were observed.

New insights into paediatric regional anaesthesia: new drugs.

Over the years paediatric regional anaesthesia has gained a worldwide consensus, and it can now be considered a significant part of perioperative pain control in children. As in many fields, with the use of drugs administered epidurally there is a fundamental need for safety and efficacy. Two new local anaesthetic agents have recently entered the market, ropivacaine and levobupivacaine, which seem to offer a wider safety margin in comparison with the old drugs as well as valid pain control. To prolong their analgesic duration, many adjuvants can be used, and clonidine and ketamine are probably the best solution. This review summarizes the most recent data on these drugs and their use in children.

[S(-) bupivacaine (levobupivacaine) in peripheral blocks: preliminary results]. / S(-) bupivacaina (levobupivacaina) nei blocchi periferici: risultati prelminari.

We have compared the onset time, anesthetic potency and adverse effects of three local anaesthetics (ropivacaine, levobupivacaine and bupivacaine) in two type of peripheral blocks (brachial plexus block for upper limb and femoral nerve block for lower limb) in adult patients in a double blind, randomized, prospective study. A total of 66 patients undergoing orthopaedic surgery were randomly allocated to receive brachial plexus block or femoral nerve blockade with 0,5% ropivacaine (group R, n=22), 0,5% levobupivacaine (group L, n=22) or 0,5% bupivacaine (group B, n=22), each groups has been divided into two subgroups (LBP n=11, RBP n=11, BPB n=11, LBF n=11, RBF n=11, BBF n=11) dipending on the type of block. The onset of sensory nerve block was similar for the three groups; the onset of motor block and onset time ready to surgery were faster in group R (-30%) if compared with group L and B. The duration of motor block and sensory block was respectively longer in group L and in group B. Study results have not been influenced by the blocks, except for plexus nerve block where we observed the same results for group B and group R in relation to onset time ready to surgery. VRS scores were higher in group R as showed by the number of analgesic request in postoperative period. We did not observe any adverse effect. We conclude that ropivacaine acts faster with less interpatient variability, while levobupivacaine and bupivacaine offer a prolonged postoperative analgesia. For this reason, with the exception of bupivacaine due to major cardio and neuro toxicity, we can indifferently use levobupivacaine or ropivacaine depending on the requested characteristics of the anesthetic.

Spinal anesthesia in children: pro.

Spinal anaesthesia, first introduced in children at beginning of 20th century, offers adequate intraoperative anaesthetic conditions (analgesia and muscle relaxation). The technique is easy to perform even if lumbar puncture is more difficult when the children is smaller. It has not been observed haemodynamic modifications especially in patients under 5 year of age; duration of spinal anaesthesia is shorter if compared to adults and post dural puncture headache (PDPH) after spinal anaesthesia is as common in children as it is in adults, but was usually mild and very short lasting. PDPH has not been correlated with the type of spinal needle used. Hyperbaric solution of local anaesthetics like bupivacaine and tetracaine are preferable. The only adjuvant used for spinal anesthesia in children is morphine, which should be administered only in patients admitted to high dependency unit in the postoperative period. Spinal anaesthesia is indicated mainly in sub umbilical surgical procedures lasting no more than 90 minutes and particularly in the surgical treatment of former premature infants who present an higher risk with regional anaesthesia.

Ropivacaine-clonidine combination for caudal blockade in children.

BACKGROUND: Adding clonidine to weak ropivacaine solutions (<0.2%) could potentially enhance analgesia as well as further reduce the risk for unwanted motor blockade. The aim of the present study was to compare the postoperative pain-relieving quality of a ropivacaine 0.1%-clonidine mixture to that of plain ropivacaine 0.2% following caudal administration in children. METHODS: In a prospective, observer-blinded fashion, 40 ASA 1 paediatric patients undergoing subumbilical surgery were randomly allocated to receive a caudal injection of either plain ropivacaine 0.2% (1 ml/kg) (R0.2) or a mixture of ropivacaine 0.1% with clonidine 2 microg/kg (1 ml/kg) (R0.1C). Objective pain scale score and need for supplemental analgesia were used to evaluate analgesia during the first 24 h postoperatively. Residual postoperative sedation was also assessed. RESULTS: A significantly higher number of patients in the R0.1C group (18/20) could be managed without supplemental analgesia during the first 24 h postoperatively compared to the R0.2 group (11/20) (P=0.034). Both the degree and the duration of postoperative sedation was similar in both groups. No signs of postoperative motor blockade were observed. CONCLUSIONS: The combination of clonidine (2 microg/kg) and ropivacaine 0.1% is associated with an improved quality of postoperative analgesia compared to plain 0.2% ropivacaine. The improved analgesic quality of the clonidine-ropivacaine mixture is achieved without causing any significant degree of postoperative sedation.

Ropivacaine vs bupivacaine in major surgery in infants.

PURPOSE: To assess and compare the onset time and duration of neuroblockade obtained after ropivacaine or bupivacaine in infants undergoing major abdominal surgery. We also evaluated the efficacy and safety of employing ropivacaine instead of bupivacaine to provide operative anesthesia and postoperative analgesia. METHODS: In a prospective double blind study 28 infants, aged 1-12 months, undergoing elective major abdominal surgery, were randomly allocated to receive, after induction of general anesthesia, either 0.7 ml x kg(-1) bupivacaine 0.25% (group B) or ropivacaine 0.2% (group R) via lumbar epidural block. The onset time, total surgical time and duration of analgesia were recorded. RESULTS: No differences were noted in demographic data, hemodynamic variables or duration of surgery. The onset time for sensory blockade was 13.1 min +/- 2.1 (group B) and 11.7 +/- 2.4 min (group R). The duration of analgesia was 491 +/- 291 (group R) and 456 min +/- 247 (group B). Eight patients in group B and six in group R needed codeine and acetaminophen rescue on at least one occasion during the 24 hr study period. No major side effects were noted in either groups. CONCLUSIONS: In infants undergoing major abdominal surgery under combined epidural/light general anesthesia, ropivacaine 0.2% produces sensory and motor blockade similar in onset, duration of action and efficacy to that obtained from an equal volume, 0.7 ml x kg(-1), of bupivacaine 0.25%.

A clinical comparison between needle-through-needle and double-segment techniques for combined spinal and epidural anesthesia.

BACKGROUND AND OBJECTIVES: The goal of the present investigation was to compare the double-segment and the needle-through-needle techniques for combined spinal and epidural anesthesia (CSE) in a prospective, randomized, blinded study. METHODS: With Ethical Committee approval and patient's consent, 120 patients were randomized to receive CSE by the needle-through-needle (SST; n=60) or the double-segment technique (DST; n=60). A blind observer measured the time required from skin disinfection to readiness for surgery (loss of pinprick sensation up to T10), failure of dural puncture, need for epidural top-up before surgery, patient acceptance, and occurrence of complications. RESULTS: No neurologic complications were observed in either group. Time to readiness for surgery was 22.7+/-8.2 minutes in the SST group and 29.8+/-8.31 minutes in the DST one (P < .001). Dural puncture was unsuccessful in three patients in the SST group (5%) and in one patient in the DST group (1.6%) (ns); inadequate spread of spinal anesthesia was observed in five patients in the SST group (8.3%) and in eight patients in the DST group (13.3%) (ns). No difference in the incidence of hypotension, postdural puncture headache, and back pain was observed between the two groups. Acceptance of anesthetic procedure was better in the SST (85%) than in the DST group (66.6%) (P < .05). CONCLUSIONS: The needle-through-needle technique for CSE requires less time, has no greater failure rate, and results in greater patient satisfaction than the double-segment technique. The use of a spinal needle with an adjustable locking mechanism and protruding up to 15 mm beyond the Tuohy needle improved successful spinal block in the needle-through-needle technique compared with previous reports.

Spinal anesthesia with clonidine and bupivacaine in young humans: interactions and effects on the cardiovascular system.

BACKGROUND: Clonidine, an alpha 2 agonist, is known to prolong the action of local anesthetics, and to provide a satisfactory analgesia; hypotension and bradycardia have been observed after its intrathecal administration. The aim of our study was to determine whether intrathecal administration of clonidine can reduce the dose of local anesthetic, and the effects of clonidine on the cardiovascular system, and on arousal level. METHODS: In a prospective, randomized study we evaluated 56 patients scheduled for minor surgical procedure (spermatic vein ligature) under unilateral spinal anesthesia with hyperbaric bupivacaine 1%. One half of patients received clonidine (105 micrograms) in addition to bupivacaine. Mean arterial pressure, heart rate were recorded baseline until 1 hour after surgery. Cardiac output, stroke volume, ejection fraction, systemic vascular resistance and left cardiac work were measured, by thoracic electric bioimpedance method, baseline until 1 hour after surgery. Sensory block, motor block and sedation level were measured at the beginning of anesthesia and for 6 hours after the end of surgery. RESULTS: In the clonidine treated group we did not observe variations of cardiovascular parameters; in the same group we did observe sensory block and motor block significantly prolonged, a higher sedation level and a significant postoperative analgesia. CONCLUSIONS: In summary, the addition of clonidine to hyperbaric bupivacaine seems to be particularly useful in unilateral spinal anesthesia, exerting minimal influence on haemodynamic parameters, and guaranting a satisfactory postoperative analgesia.

[Sedation, combined anesthesia, and total intravenous anesthesia (TIVA) with propofol in the pediatric surgical patient]. / Sedazione, anestesia combinata e anestesia totalmente endovenosa (TIVA) con propofol nel paziente chirurgico pediatrico.

Total intravenous anaesthesia (TIVA) has recently obtained a wide diffusion in paediatrics, thanks to the pharmacological properties of propofol. The authors make a review on sedation, combined anaesthesia and Tiva in paediatric anesthesia, particularly on propofol and its characteristics. They describe the practical use of TIVA with recent knowledge in this field.

Clonidine-mepivacaine mixture vs plain mepivacaine in paediatric surgery.

In a double-blind study, 42 children, aged 1-10, undergoing general subumbilical surgery, were randomly allocated to two groups; they received, via caudal extradural, 1% mepivacaine 7 mg.kg-1 and normal saline 1 ml (Group 1) and a mixture of 1% mepivacaine 7 mg.kg-1 plus clonidine 2 micrograms.kg-1 and normal saline up to 1 ml (Group 2) respectively. No significant difference was noticed in age, weight, duration of surgery and onset time of anaesthesia, blood pressure, heart rate and oxygen saturation. Mean duration of analgesia (evaluated with 'Broadman objective pain scale') was 143 min for Group 1 and 218 min for Group 2 (P < 0.05); the time of sedation (evaluated with a sedation score) was statistically longer in Group 2 (172 min vs 89 min in Group 1). This longer sedation is due both to the longer analgesia and partially to a side effect of clonidine. In conclusion the addition of 2 micrograms.kg-1 of clonidine to mepivacaine prolongs the duration of caudal analgesia in children.